Key words/Related terms and notions on the topic: thyroid gland (thyroid), thyroid hormones

(T4, T3), free T4and T3 indices, thyroid-stimulating hormone (TSH), thyroid binding globulin (e.g.,
thyroglobulin (TBG)), TSH-binding inhibitor immunoglobulin, antimicrosomal and
antithyroglobulin antibodies, hypothyroidism, multinodular goiter, nonspecific lymphocytic
thyroiditis, Hashimotos thyroiditis, subacute granulomatous thyroiditis (DeQuervains thyroiditis),
Riedels thyroiditis, thyrotoxicosis, diffuse toxic goiter (Graves disease), exophthalmos, thyroid
tumors, follicular adenoma, papillary carcinoma, anaplastic carcinoma, follicular carcinoma,
medullary carcinoma, fine needle aspiration cytology.
HYPOTHYROIDISM (MYXEDEMA)
It is the characteristic reaction to thyroid hormone deficiency. The spectrum of hormone ranges
from a few non specific symptoms to overt hormone, to myxedemal coma. Hypothyroidism
occurs in 3 to 6 for the adult population, but is symptomatic only in a minor of them. It occurs 8 to
10 times more often in woman than in men and usually develops after the age of 30.
Classification
A. 1. Congetial.
2. Acquired:
1) Primary (thyroid gland disturbances).
2) Secondary (due to pituitary disease).
3) Tertiary (due to hypothalamic disease).
4) Peripheral.
Etiology
A cause is usually evident from the history and physical examination.
1. Primary (thyroidal) hypothyroidism.
1) surgical removal, total thyroidectomy of thyroid carcinoma, subtotal thyroidectomy
(hypothyroidism occurs from 25 to 75 of patients in different series);
2) irradiation (hypothyroidism results from external neck irradiation therapy in doses 2000 rads
or more such as are used in the treatment of malignant lymphoma and laryngeal carcinoma);
I131 therapy for hyperthyroidism (it results in hyperthyroidism in 20 % to 60 % of patients
within the first year after therapy and in 1 % to2 % each year there after);
3) during or after therapy with propylthyouracil, methimazole, iodides or beta-blockers;
4) autoimmune processes (hypothyroidism usually occurring as a sequel to Hashimotos
thyroiditis and results in shrunken fibroid thyroid gland with a little or no function and
infiltrative diseases (tuberculosis, actynomycosis);
5) trauma;
6) iodine deficiency.
2.Secondary and tertiary hypothyroidism
It occurs due to either deficient secretion of TSH from the pituitary or lack of secretion of TRH
from the hypothalamus.
Tumor;
Infarction;
Infiltrative process;
Trauma;
Drugs (reserpin, parlodel).
3. Peripheral hypothyroidism:
- peripheral tissue resistance to thyroid hormones;
- decreasing of T4 peripheral transformation into T3 (in liver or in kidneys);
- production of antibodies to thyroid hormones.

Congenital:
- Maldevelopment hypoplasia or aplasia;
- Inborn deficiencies of biosynthesis or action of thyroid hormone;
- Atypical localization of thyroid gland;
Classification. (cont.)
B. 1. Laboratory (subclinical) hypothyroidism.
2. Clinical hypothyroidism, which can be divided on stages of severity: mild, moderate, severe.
C. 1. Compensation.
2. Subcompensation.
3. Decomposition.
D. 1. Without complications.
2. With complications (myopathy, polyneuroparhy, encephalopathy, coma).
Clinical Findings of Hypothyroidism
The most common features of hypothyroidism include fatigue, dry skin, cold intolerance,
constipation, menstrual irregularities and possibly weight gain.
The major symptoms and signs of hypothyroidism reflect showing
Virtually every organ system can be affected. The onset of symptoms
severity varies considerably and correlates poorly with biochemical
manifestations of hypothyroidism are non-specific, the diagnosis is
overlooked in patients with other chronic illnesses and elderly.

of physiologic function.
may be rapid or gradual,
changes. Because many
particularly likely to be

Metabolic system
Hypothermia is common. Hyperlipidemia with increase of serum cholesterol and trigliceride occurs
because of reduced lipoprotein lipase activity.
Skin and Appendages
Thyroid deficiency results in dry, thick and silk skin, which is often cool, pale, waxy due to
vasoconstriction, increase in carotene concentration and anemia, rough epidermis. Skin may be
orange due to accumulation of carotene. Non-pitting puffiness is due primarily to the accumulation
in skin and subcutaneous tissues of a mixture of mucopolysaccharides, hyaluronic acid and
chondroitin sulphate (glycosoamynoglicanes, mainly hyaluronic acid), which are highly hydrophilic
and retain sodium and water. So, there is nonpitting edema of the hands, feet and periorbital regions
(myxedema). The faces are puffy and features are coarse. Hair may become course and brittle, hair
growth slows and hair loss may occur especially from the temporal aspect of the eyebrows.. Lateral
eyebrows thin out and body hair is scanty. Decreased activity of sebaceous glands contributes to the
dry skin.
Ocular manifestations
Baggy swelling of upper and lower eyelids.
Cardiovascular
Bradycardia, impaired muscular contraction, cardiac output, quiet heart sounds, a flabby
myocardium, pericardial effusion, cardiac wall is thick, it is increased by interstitial edema.
Increased peripheral resistance may result in hypertension. (These findings, along with peripheral
edema, may simulate congestive heart failure). Cardiomegaly and pericardial effusion may be
present. Effusion is the result of increased capillary permeability and is rich in protein and
cholesterol. Pleural and peritoneal effusions also may be encountered. Angina may occur due to

coronary artery disease upon initiation of thyroid replacement. Angina symptoms, when present,
characteristically occur less often after the onset of hypothyroidism, probably because of decreased
activity.
ECG may show low voltage and/or non-specific ST segment and T wave changes (P, QRS, T,
isoelectric S-T). T may be inverted. Incomplete right bundle branch block common.
AST, ALT, LDH, CPK may be elevated reflecting diminished catabolism and probably increased
cellular "leakage" of the enzymes. Hypercholesterolaemia is common. Total and LDL cholesterol
are elevated, probably reflecting diminished catabolism. There is evidence to suggest that incidence
of coronary atherosclerosis is elevated in hypothyroidism.
Pulmonary
Reduced excretion of a water load may be associated with hyponatriemia. Renal blood flow and
glomerular filtration rate are reduced, but serum creatinine is normal. May be mild proteinuria and
infections of urinary tract.
Ear, Nose, Throat
Partial deafness may be seen, due to increased mucopolysaccharides in the middle ear. Nasal
obstruction and discharge for the same reason. Husky voice due to infiltration, but not paralysis of
vocal cords. Enlarged tongue may also contribute to garbled voice and sleep apnea/snoring.
Gastrointestinal
Appetite is reduced. Hypothyroidism does not cause obesity, but modest weight gain from fluid
retention and fat deposition often occurs. Intestinal peristalsis is reduced. Decrease of
gastrointestinal motility leads to constipation, flatulence and abdominal distension (may be caused
by ascities as well). Ascitic fluid, like other serous effusions in myxedema, has high protein content.
Megacolon (uncommon) with signs of paralytic ileus. Malabsorption syndrome may be seen
occasionally. Atrophic gastritis common, resulting in achlorhydria (50% of patients). B12
absorption decreases and pernicious anemia is present in 12% of patients. Achlorhydria occurs,
often associated with pernicious anemia.
Parietal antibodies increased in 1/3 of patients.
Nervous System
Thyroid hormone is essential in nervous tissue development. Children born hypothyroid suffer from
severe brain damage (cretinism). The earlier the initiation of treatment, the better the results for
normal intellectual development. Decreased concentration, lethargy and coma may be seen in
adults. Sedatives (morphine, barbiturates, etc.) may precipitate C02 narcosis and coma.
Most of hypothyroid patients complain of fatigue, loss of energy, lethargy, forgetfulness, reduced
memory. Their level of physical activity decreases, and they may speak and move slowly. Mental
activity declines and there is inattentiveness, decreased intellectual function, and sometimes may be
depression.
Neurological symptoms include also hearing loss, parasthesias, objective neuropathy, particularly
the carpal tunnel syndrome, ataxia.
Reflexes are characteristically slow (relaxation phase) due to decreased muscle function. Tendon
reflex shows slowed or hung-up relaxation. Carpal tunnel syndrome may be seen.
Muscles
Stiffness, aching, cramps very common. Enzymes CPK and SGOT may be elevated.

Skeleton
T4 and growth hormone act synergistically to promote skeletal maturation. Lack of thyroid
hormone in childhood results in stippled epiphyses (enichyseal dysgenesis). Alkaline phosphatase is
decreased in hypothyroid children, as compared to normal. Adults have symptoms reminiscent of
degenerative arthritis.
Muscle and joint aches, pains and stiffness are common. Objective myopathy and joint swelling or
effusions are less often present. The relaxation phase of the tendon reflexes is prolonged. Serum
creatine phosphokinase and alanine aminotransferase activities are often increased, probably as
much to slowed enzyme degradation as to increased release from muscle.
Hemopoetic system
There are various types of anemia, most common is mild normochromic, normocytic anemia.
Microcytic (from iron deficiency due to impaired intestinal absorption) or macrocytic (B12 or folic
acid deficiency) due to concomitant pernicious anemia or malabsorption. Anemia, usually
normocytic, caused by decreased red blood cell production, may occur. It is probably from
decreased need of peripheral oxygen delivery rather than hematopoetic defect. Megaloblastic
anemia suggests coexistent pernicious anemia. Most patients have no evidence iron, folic acid or
cyancobalamin deficiency.
Renal and Electrolytes
Glomerular filtration rate, renal plasma flow, and tubular reabsorption are reduced, but creatinine
and BUN are normal. Water excretion is impaired and fluid administration intravenously should be
carefully monitored as it may result in water intoxication in patients with myxedema. Na can be
decreased in serum and gives rise to a condition similar to that found with the syndrome of
inappropriate secretion of ADH (SIADH). Total body water may be increased due to
mucopolysaccharide retention of H20.
Endocrine system
There may be menorrhagia (from anovulatory cycles), secondary amenorrhea, infertility and rarely
galactorrhea. Hyperprolactinemia occurs because of the absence of the inhibitory effect of thyroid
hormone on prolactine secretion (and causes galactorrhea and amenorrhea or Van Vik Cheness
Rosss syndrome).
Pituitary-adrenal function is usually normal. Pituitary enlargement from hyperplasia of the
thyrotropes occurs rarely in patients with primary hypothyroidism such enlargement also may be
caused by a primary pituitary tumor, which resulting TSH deficiency.
Enlargement of thyroid gland in young children with hypothyroidism suggests a biosynthetic defect.
Hypothyroidism in adults is caused by Hashimoto thyroiditis.
Secretion of growth hormone is deficient because thyroid hormone is necessary for synthesis of
growth hormone. Growth and development of children are retarded. Epiphyses remain open.
Subclinical (laboratory) hypothyroidism.
It is a state in which we cant find clinical features of hypothyroidism and euthyroidism is reached
by compensatory increasing of TSH secretion and thats why synthesis and secretion of such level
of thyroid hormone that will be enough for organism. It is an asymptomatic state in which serum T4
and free T4 are normal, but serum TSH is elevated. The therapy may provide the patient with more
energy, a feeling of well being, desirable weight reduction, improved bowel function or other signs
of better health even though the patient is not aware of these symptoms before therapy.
Diagnostic of hypothyroidism is based on:
1) history;

2) clinical features;
3) blood analysis: anemia; hypercholesterolemia;
4) levels of thyroid hormone: both serum T4 and T3 are decreased (but in 25% of patients with
primary hypothyroidism may be normal circulating levels of T3);
5) ECG;
6) examination of tendon reflexes;
7) ultrasonic examination.
Differential diagnosis of primary and secondary hypothyroidism:
1) clinical features:
Secondary hypothyroidism is not common, but it often involves other endocrine organs affected
by the hypothalamic pituitary axis. The clue to secondary hypothyroidism is a history of
amenorrhea rather than menorrhagia in a woman with known hypothyroidism.
In secondary hypothyroidism, the skin and hair are dry but not as coarse; skin depigmentation is
often noted; macroglossia is not prominent; breasts are atrophic; the heart is small without
accumulation of the serous effusions in the pericardial sac; blood pressure is low, and
hypoglycemia is often found because of concomitant adrenal insufficiency or growth hormone
deficiency.
2) laboratory evaluation:
shows a low level of circulating TSH in secondary hypothyroidism, whereas in primary
hypothyroidism there is no feedback inhibition of the intact pituitary and serum levels of TSH
are very high. The serum TSH is the most simple and sensitive test for the diagnosis of pituitary
hypothyroidism.
Serum cholesterol is generally low in secondary hypothyroidism, but high in pituitary
hypothyroidism.
Other pituitary hormones and their corresponding target tissue hormones may be low in
secondary hypothyroidism.
The TSH test is useful in distinguishing between secondary and tertiary hypothyroidism in the
former; TSH is not released in response to TRH; whereas in the later, TSH is released.
Treatment of hypothyroidism.
1. Diet 10.
2. Regimen is not restricted.
3. 1) replacement therapy:
- desiccated animal thyroid (this is an extract of pig and cattle thyroid glands, which
standardized based on its iodine content but they are too variable in potency to be reliable
and should be avoided);
- synthetic preparations of :
T4 (l-thyroxine)
- T4 is preparation of choice, because it produces stable serum levels of both T4 and T3.
- Absorption is fairly constant 90 to 95% of the dose. T3 is generated from T4 by the liver.
- The initial dosage can be 1.6 mkg/kg of ideal weight or 12.5-25 mkg in older patients and
25-50 mkg in young adult.
- The dosage can be increased in 25-50 mkg increments at 4 to 6 week intervals until
clinical and biochemical euthyroidism is achieved. In older patients more gradual
increments are indicated. Cautious replacement is particularly warranted in patients with
ischemic heart disease, because angina pectoris or cardiac arrhythmia may be precipitated
by T4 therapy.

The average maintenance dosage is 100 to 150 mkg/day orally, only rarely is a larger
dosage required. In general, the maintenance dose may decrease in the elderly and may
increase in pregnancy.
The dosage should be minimum that restores TSH levels to normal (though this criterion
cannot be used in patients with secondary hypothyroidism).
Patient takes the whole dose of T4 once a day (in the morning), in the summer the dose
may be decreased and in the winter should be increased.

T3 (liothyronine sodium) should not be used alone for long-term replacement because its rapid
turnover requires that it be taken. T3 is occasionally used mainly in starting therapy because
the rapid excretion is useful in the initial titration of a patient with longstanding
hypothyroidism in whom cardiac arrhythmia may occur early in replacement therapy. The risk
of jatrogenic hyperthyroidism is therefore greater in patients receiving these preparations.
In addition, administering standard replacement amounts of T3 (25 to 50 mkg/day) results in
rapidly increasing serum T3 levels to between 300 and 1000 mkg within 2 to 4 h, these levels
return to normal by 24 h. Therefore, when assessing serum T3 levels in patients on this
particular regimen, it is important for the physician to be aware of the time of prior
administration of the hormone. Additionally, patients receiving T3 are chemically
hyperthyroid for at least several hours a day and thus are exposed to greater cardiac risks.
Similar patterns of serum T3 concentrations are seen when mixtures of T3 and T4 are taken
orally, although the peak levels of T3 are somewhat lower. Replacement regimes with
synthetic preparations of T4 reflect a different pattern of serum T3 response increases in
serum T3 occur gradually over weeks, finally reaching a normal value about 8 wk. after
starting therapy.
Synthetic T3 and T4 combinations (liotrix, thyreocomb). These preparations were developed
before it was appreciated that T4 is converted to T3 outside of the thyroid.
These preparations should not be used.

2) Symptomatic therapy:
- beta-blockers (should be used in patients with tachycardia and hypertension) in the
dose of 20 40 - 60 mg/day;
- hypolypidemic agents;
- vitamins (A, B, E);
- diuretics and others.
Myxedema Coma
Myxedema coma (decompensated hypothyroidism) is the end stage of severe long-standing
hypothyroidism, in which mental obtundation is profound. This is one of the few endocrine
emergencies as the mortality is over 50%. This state often affects the elderly patient, occurs most
commonly during the winter, and is usually accompanied by a subnormal temperature. Bradycardia
and hypotension are present.
Predisposing factors are always present and include cold, infection, trauma, and CNS depressants.
Alveolar hypoventilation leading to C02 retention and narcosis, dilutional hyponatremia resembling
inappropriate ADH secretion are common. The clinical diagnosis is often difficult. Elderly patients
with various illnesses may resemble patients with myxedema and, after brain stem infarction, they
may become comatose and hypothermic. The diagnosis should be made on clinical grounds and
therapy initiated without awaiting the results of thyroid function tests.

It is a life-threatening complication of hypothyroidism, which is extremely rare in warm climates

but not uncommon in cold areas.
Precipitating factors include:
- exposure to cold;
- infection;
- trauma;
- drugs that suppress the CNS.
Myxedema coma characteristics include a background of long-standing hypothyroidism with
extreme hypothermia (temperatures 24 to 32), areflexia, seizures, CO2 retention, and respiratory
depression caused by decreased cerebral blood flow. Severe hypothermia may be missed unless
special low reading thermometers are used. Rapid diagnosis (based on clinical judgement, history,
and physical examination) is imperative because early death is likely.
Treatment of myxedema coma.
It is treated with large doses of T4 (250-500 mkg I/v bolus 3 4 times a day) or T3 if available (40
100 mkg I/v bolus 3 times a day), because TBG must be saturated before any free hormone is
available for response. The maintenance dose for T4 is 50 mkg/day I/v and for T3 10 20 mkg/day
I/v until the hormone can be given orally.
The patient should not be rewarmed rapidly because of the threat of cardiac arrhythmia.
Hypoxemia is common, so PaO2 should be measured at the outset of treatment. If alveolar
ventilation is compromised, immediate mechanical ventilatory assistance is required.
THYROIDITIS
The various types of thyroiditis encompass a heterogeneous group of inflammatory disorders of
diverse etiologies and clinical features. With all forms of thyroiditis, destruction of the normal
architecture of the thyroid follicular occurs, yet each disorder has distinctive histologic
characteristics. For the purposes of understanding the clinical manifestations, thyroiditis is
classified according to either the severity or duration of illness using the following scheme:
1. Acute thyroiditis.
2. Subacute thyroiditis:
- subacute granulamatous thyroiditis;
- subacute lymphocytous thyroiditis.
3. Chronic thyroiditis:
- Hashimoto thyroiditis;
- Ridel struma.
4. Specific thyroiditis.
5. Thyroiditis caused by mechanical or physical factors.

Acute thyroiditis
Etiology
Acute thyroiditis it is an acute bacterial inflammation due to a bacterial pathogen, most commonly
staphylococcus aureus, streptococcus hemolytica,streptococcus pneumonie, of anaerobic
streptococcal organisms. Infection due to other bacterial pathogens, such as salmonella and
escherichia coli have been reported, as well as fungal infections such as coccidiodomycosis.
Infection occurs either secondary to hematogenous or lymphatic spread, or as a result of direct
introduction of an infective agent by trauma. Persistent thyroglossal duct abnormalities have also
been associated with acute thyroiditis.

Clinical features
Fever, chills and other systemic signs or symptoms of abscess formation are present. Anterior neck
pain and swelling are usual, with pain occasionally radiating to the ear or mandible.
The physical examination suggests the presence of an abscess, with erythema of the skin, marked
tenderness to palpation, and at times fluctuance.
Laboratory tests
Leucocytosis with a left shift, increased ESR are usually present. Thyroid hormone concentrations
in blood are normal, although hyperthyroxinemia has been reported.
Treatment
Patient should be treated at surgical department. Parental antibiotics should be administered
according to the specific pathogen identified. If fluctuance is present, incision and drainage might
be required. Bacterial thyroiditis must be treated early and aggressively, since abscess formation
can occasionally dissect downward into the mediastinum. Recurrences of the disorder are very rare.
(Duration of the treatment must be nearly 1,5-2 month).

Subacute thyroiditis
It is an acute inflammatory disease of the thyroid probably caused by a virus.
Subacute granulomatous thyroiditis (giant cell thyroiditis) SAT.
Etiology
SAT is most likely viral in origin .The specific agent responsible for the disorders is not known,
although coxsackie virus, adenovirus and the mumps, echovirus, influenza and Epstein-Barr viruses
have been implicated in the etiology.
A genetic predisposition is likely because of the association of HLA-BW 35 histocompatibility
antigens.
Clinical features
The most common symptom is unilateral anterior neck pain, often associated with unilateral
radiation of pain to the ear or mandible. Pain is often proceeded by a few weeks prodrome of
myalgias, low-grade fever, malaise and sore throat. Dysphagia is also common. Symptoms of
hyperthyroidism (such as tachycardia, weight loss, nervousness, and diaphoresis occur in up to 50%
of patients as the disorder processes, pain can migrate to the contralateral side.
Physical examination discloses an exquisitely tender, very hard, nodular enlargement, which is
most often unilateral. Tenderness is often so extreme that palpation is limited. Bilateral tenderness
and goiter can occur as well. Tachycardia, a widened pulse pressure, warm skin and diaphoresis are
also observed when hyperthyroidism is present.
Laboratory findings.
Early in the disease we can find an increase in T4, a decrease in RAI uptake (often 0), leucocytosis
and a high ESR. After a several weeks, the T4, is decreased and the RAI uptake remains low. Full
recovery is the rule; rarely, patients may become hypothyroid.
Treatment
An acute phase lasts from 4-8 weeks, during which treatment is symptomatic (aspirin 600 mg q 3-4
h, prednisolone 10-20 mg orally tid; after 1 week prednisolone can be tapered by 5 mg every 2-3
days; thus glucocorticoids are usually not required for longer than several weeks. Symptoms of
hyperthyroidism are effectively controlled by the use of beta-blockers).

Following the acute phase euthyroidism is restored, and the thyroid becomes depleted of stored
hormone. Patients can either remain euthyroid or progress to hypothyroid phase. It rarely lasts
longer than 2-3 months, and during this phase thyroid hormone replacement in the form of
levothyroxine 0,10-0,15 mg/day should be given. After several months of treatment T4 can be
discontinued.
Following the hypothyroid phase recovery occurs, and the normal histologic features and secretory
capacity of the thyroid are restored.
Subacute lymphocytic thyroiditis (silent thyroiditis) A subacute disorder occurring most commonly
in women , often in the postpartum period, characterized by a variable, but mild degree of thyroid
enlargement, absence of thyroid tenderness, and self-limited hyperthyroid phase of several weeks to
several months, often followed by transient hypothyroidism but with eventual recovery to the
euthyroid state.
Etiology
Recent evidence suggests on:
1) autoimmune component (because of autoantibodies observed);
2) genetic predisposition (this is a significant prevalence of HLA-DRW3 and HLA-DRW5
histocompatibility agents);
3) viral etiology (viral antibody titers are rarely elevated).
Clinical features.
Hyperthyroid symptoms are frequent and vary from mild to normal. (Postpartum thyroiditis occur 6
weeks to 3 months after delivery).
Physical examination usually discloses a mildly enlarged, diffuse, firm, nontender goiter it has been
reported that up to 50 % of patients do not have goiter.
Laboratory findings
Serum total and free T4 and T3 are elevated. Biopsies reveal lymphocytic infiltration as seen in
Hashimotos thyroiditis.
Thyroid autoantibodies are positive in greater than 50 % of patients.
Treatment
Hyperthyroid phase lasts from 6 weeks to 3 month. Treatment is conservative, usually requiring
only B-adrenergic blockers with propranolol. Euthyroid interval lasts for 3-6 weeks. During
hypothyroid period (it usually lasts no longer than 2-3 months thyroid hormone supplementation
with T4 0,10-0,15 mg/day may be required. Following the hypothyroid phase patients usually
remain clinically euthyroid.)

Chronic thyroiditis
Hashimoto thyroiditis (chronic lymphocytic thyroiditis) HT
Etiology
HT is an organ - specific autoimmune disorder, a chronic inflammation of the thyroid with
lymphocytic infiltration of the gland generally though to be caused by autoimmune factors.
It is mire prevalent (8:1) in woman than men and is most frequent between the ages of 30 and 50 . A
family history of thyroid disorders is common, and incidence is increased in patients with
chromosomal disorders, including Turners, Down and Klinefelters syndromes. Histologic studies
reveal extensive infiltration of lymphocytes in the thyroid.

The basic defect underlying this disease suggests an abnormality in suppressor T lymphocytes that
allows helper T lymphocytes to interact with specific antigens directed against the thyroid cell. A
genetic predisposition is suggested because of the frequent occurrence of the HLA- DR5
histocompatibility antigen in patients with HT.
Clinical features
HT is characterized by a wide spectrum of clinical features, ranging from no symptoms and the
presence of small goiter to frank myxedema.
Occasionally patients complain of a vague sensation of tightness in the area of the anterior neck or
mild dysphagia. In general, however, thyroid enlargement is insidious and asymptomatic.
Symptoms of hypothyroidism may or may not be present, depending on the presence or absence of
biochemical hypothyroidism.
Physical examination usually discloses a symmetrically enlarged, very firm goiter, a smooth or
knobby consistency is common. Occasionally patients present with a single thyroid nodule.
A small group of patients have a form of HT termed primary idiopathic hypothyroidism, goiter is
usually absent in this group.(atrophic form of HT).
Yet a small subset of patients(probably 2-4%) present with hyperthyroidism and have so-called
hashitoxicosis (hypertrophy from of HT).
Laboratory findings
1) early in the disease a normal T and high titers of antithyroid (antimicrosomal) antibodies,
peroxidase antibodies can be detected. Late in the disease, the patient develops hypothyroidism
with a decreased in T and antibodies in this stage are usually no longer detectable;
2) the thyroid scan typically shows a irregular pattern of iodine uptake;
3) fine-needle biopsy of the nodule or enlarging area should be done to rule out a coexistent
neoplasm.
Treatment
1) treatment of HT requires lifelong replacement with thyroid hormone to correct and prevent
hypothyroidism. The average oral replacement dose with l-thyroxine is 100 to 150
mkg/day;
2) glucocorticoids have been reported to be effective in HT when true is a rapidly enlarging
goiter associating with pressure symptoms;
3) symptomatic therapy
Ridel thyroiditis
Etiology
This extremely rare inflammatory disorder is of uncertain etiology, and earlier suggestions that it
might be a fibroid variant of HT have not been substained.
Clinical features
Clinically, Ridel thyroiditis presents with pressure symptoms, and on examination an extremely
hard , immobile thyroid gland is palpated The thyroid can be uniformly enlarged, or only one lobe
might be affected. The disorder can be associated with other focal sclerosing symptoms, including
retroperitoneal and mediastenal fibrosis and ascending cholecystitis.
Laboratory findings
1. Thyroid function tests show hypothyroidism in approximately 25 % of patients.
2. Thyroid antibodies are usually negative.
3. The thyroid scan shows decreased uptake in involved areas.

Treatment
- is surgical for those patients in whom symptoms of obstruction occur.
- thyroid hormone is required for treatment of hypothyroidism, but thyroid hormone alone will
not result in goiter shrinkage.
Characteristic Features of Thyroiditis
Classic Pattern of
Other Clinical
Form of
Presumed
Thyroid
Manifestations
Thyroiditis
Etiology
Dysfunction
Autoimmune T cell mediated Hypothyroidism
Firm small-toautoimmunity
medium goiter
Painless small
Lymphocytic T cell mediated Transient
goiter
thyrotoxicosis
(painless, silent, autoimmunity?
followed by
postpartum)
hypothyroidism

Treatment

Thyroxine for
hypothyroidism
Observation, beta
blockade for
thyrotoxicosis,
thyroxine for
hypothyroidism
Painful and
Subacute (de
Viral infection?
Transient
NSAID or
tender hard goiter glucocorticoid, beta
Quervain)
thyrotoxicosis
followed by
blockade for
hypothyroidism
thyrotoxicosis,
thyroxine for
hypothyroidism
Acute
Bacterial, fungal, Thyroid dysfunction Painful, tender, Antibiotic therapy,
surgical drainage
(suppurative) and protozoal
(rare)
and inflamed
infections
goiter
Amiodarone- Iodine-induced
Thyrotoxicosis
Normal-size
Thionamide antithyroid
induced type 1 hyperthyroidism
nontender gland medication
Transient
Normal-size
Glucocorticoids
Amiodarone- Inflammatory
nontender gland
induced type 2 thyroiditis, precise thyrotoxicosis
cause unknown
Riedel (invasive Idiopathic fibrosis?, Hypothyroidism in Enlarging, hard, Surgery,
glucocorticoids,
fibrous)
autoimmune?
one third of patients fixed mass
tamoxifen
* NSAID nonsteroidal anti-inflammatory drug
Parathyroid glands
Usually, 4 parathyroid glands develop, although approximately 10% of people may have 2, 3, or 5
glands. The superior glands are typically located on the posterior aspect of the upper thyroid,
whereas the location of the inferior glands is more variable. The inferior glands may be posterior to
the inferior aspect of the thyroid or ectopically located in the thyroid gland, along the carotid sheath,
or attached to the thymus. Superior glands may also be ectopic and in a retroesophageal,
retrotracheal, or retropharyngeal location. Typical parathyroid glands are approximately 5 X 3 X 1
mm.
Parathyroid hormone (PTH) is secreted by the parathyroid glands. PTH and vitamin D are the
principle regulators of Ca and phosphorus (P) homeostasis; their metabolic actions are interrelated.
PTH promotes renal formation of the active metabolite of vitamin D. Conversely, with a deficiency
of the vitamin or any resistance to its action, some of the effects of the hormone are blunted. The
most important actions of PTH are:
1) increasing the rate of bone resorption with mobilization of Ca and P from bone;
2) increasing intestinal absorption of Ca (mediated by an action on the metabolism of vitamin D);
3) stimulation of Ca resorption in the distal tubule of the kidney;

4) decreasing renal tubular reabsorption of phosphate (PO4).

These actions account for most of the important clinical manifestations of PTH excess or
deficiency.
(Calcitonin is synthesized in the C cells of the thyroid gland. The major regulator of calcitonin
secretion is the serum Ca concentration. In contrast to their effect on PTH, hypercalcemia stimulates
and hypocalcemia suppresses calcitonin secretion. A number of gastrointestinal hormones including
gastrin, glucagon, and cholecystokinin are pharmacologic secretegogues for calcitonin, but gastrin
is the most potent.
Physiologic actions:
- inhibiting osteoclastic bone resorption;
- decreasing renal tubular calcium reabsorption and others).
Normal serum calcium (Ca) levels range between 2, 25 2,75 mmol/l (8.8 10.4 mg/100 ml.
Approximately 40 % of the total blood Ca is bound to serum proteins while the remaining 50 % is
ultrafilterable and includes ionized Ca plus Ca comlexed with phosphate and citrate. The ionized Ca
fraction (about 50 % of the total blood Ca) is influenced by pH changes. Acidosis is associated with
decreased protein - binding and increased ionized Ca and alkalosis with a fall of ionized Ca due to
increased protein binding. These pH induced changes in ionized Ca occur independently of any
change in total blood Ca concentration. In the laboratory determination of serum Ca, only total
serum Ca is usually measured.
Maintenance of the blood Ca level is partially dependent upon dietary Ca intake (0,5 1,0 gm/day),
gastro-intestinal absorption of Ca, and renal Ca excretion. The major factor preserving the
constancy of blood Ca concentration is the bone Ca reservoir. About 99 % of body Ca is in bone, of
which 1 % is freely exchangeable with ECF.
HYPOPARATHYROIDISM
it is a disease resulting from PTH deficiency, characterized chemically by low serum calcium and
high serum phosphorus levels, often associated with chronic tetany.
(Pseudohypoparathyroidism is a congenital condition in which there is tissue resistance to the
effects of parathyroid hormone. It presents with skeletal abnormalities, elevated levels of serum
parathyroid hormone and normal serum calcium.)
Etiology
1) ccidental removal of or damage to several parathyroid glands during thyroidectomy (2 %);
2) radioactive iodine therapy of the hyperthyroidism or X-ray therapy of the neck organs;
3) it is also occurs as a part of a genetic syndrome of type I (hypoparathyroidism, Addisons
disease, mucucutaneous candidiasis);
4) congenital deficiency (DiGeorge syndrome), agenesis or aplasia of parathyroid glands;
5) hemorrhages, infarctions, infections of the glands;
6) severe hypomagnesemia;
7) autoimmune processes.
Classification.
1. Congenital hypoparathyroidism (aplasia of parathyroid glands).
2. Idiopathic hypoparathyroidism (autoimmune): isolated or type I autoimmune polyglandular
syndrome.
3. Post operative hypoparathyroidism.
4. Secondary hypoparathyroidism due to:
- irradiation; X-ray therapy; treatment of the thyroid gland by radioactive iodine;

infectious damaging of the glands;

hemochromatosis, granulomatous disease of parathyroids;
disturbances of the innervation or vascularization.

Due to duration:
1. Manifest hypoparathyroidism (acute and chronic).
2. Latent hypoparathyroidism.
Clinical presentation.
Patients may be asymptomatic
1. The most characteristic syndrome is tetany, resulting from severe hypocalcemia or a reduction in
the serum ionized Ca fraction without marked hypocalcemia (e.g., in respiratory or metabolic
alkalosis).
Tetany is characterized by:
1) sensory symptoms consisting of paresthesias of the lips, tongue, fingers and feet:
2) carpopedal spasm (the hands incarpal spasm adopt a characteristic position, the
metacarpophalangeal joints are flexed, the interphalangeal joints of fingers & thumb are extended
and there is opposition of the thumb), which may be prolonged or painful;
3) generalized muscle aching;
4) spasm of facial musculature;
5) laryngeal stridor.
Tetany may be overt (spontaneous symptoms) or latent. In latent tetany the neuromuscular
instability frequently is brought out by provocative tests. Trousseaus sign is carpopedal spasm
caused by reduction of the blood supply to the hand when a tourniquet or blood pressure cuff above
systolic pressure is applied to the forearm for 3 min. Chvosteks sign is contraction of the facial
muscles, elicited by a light tapping of the facial nerve. Erbas sign is dyspnea which develops after
hyperventilation.
2. Changes of other organs and systems.
1. The clinical manifestations of hypocalcemia may be primarily neurologic. Slowly developing,
insidious hypocalcemia may produce mild, diffuse encephalopathy and thus should be suspected in
any patient with unexplained dementia, depression, or psychosis.
2. Trophic changes:
- papilledema occasionally may be present and cataracts may develop after prolonged
hypocalcemia:
- changes of the skin and hair.
3. Respiratory system:
- dyspnea;
- laryngospasm.
4. Cardiovascular system:
- pain in the region of the heart like angina;
- the ECG typically shows prolongation of the Q T.
5. Gastrointestinal tract:
- spastic constipation or diarrhea.
Laboratory findings.
1. The level of total Ca < 2,2 mmol/l, ionized Ca , 1,0 mmol/l.
2. High serum PO4.
3. Low or absent urinary Ca.

Differential diagnosis have to be made with other causes of hypocalcemia:

1) increased phosphate (chronic renal failure; phosphate therapy);
2) drugs (calcitonin; diphosphanates);
3) acute pancreatitis; citrated blood in massive transfusion;
4) pseudohypoparathyroidism (resistance to PTH);
5) deficiency or resistance to vitamin D; and tetany:
1) infectious diseases (tetanus);
2) alkalosis (repeated vomiting of gastric juice; hyperventilation).
Treatment
Acute severe hypocalcemic tetany.
1. It is treated initially with IV infusion of Ca salts. 10 50 ml of 10 % solution of Ca gluconate or
Ca chloride may be given IV over 15 30 min, but the effect lasts for only a few hours. (side
effects: thrombophlebitis, IM injection can cause local necrosis).
2. Magnesium repletion.
3. Parathyroidin 1 2 ml IM 2 times a day.
4. Sedative preparations and spasmolitics.
Chronic hypocalcemia:
1. Diet with increased quantity of calcium and vitamin D.
2. Preparations of Ca and vitamin D, which have to be given orally (Calcium-D3 nicomed,
Calcemin).
3. Surgery (transplantation of a special bone into the muscles of the abdomen or back. The
efficacy is about 8 12 month).
HYPERPARATHYROIDISM
It is a generalized disorder resulting from excessive secretion of parathyroid hormone by one or
more parathyroid glands; it is usually characterized by hypercalcemia, hypophosphatemia, and
abnormal bone metabolism.
Background:
In 1891, von Recklinghausen described the classic bone disease termed osteitis fibrosa cystica. In
1925, the Viennese surgeon Mandl performed the first parathyroid exploration and adenoma
resection. Mandl noted improvement of the patient's severe skeletal abnormalities postoperatively,
linking hyperparathyroidism with bone disease. Albright later described the clinical entity of classic
primary hyperparathyroidism in the 1930s on the basis of 17 cases from his clinical practice.
Historically, the disorder was marked by characteristic skeletal changes, nephrolithiasis, and
neuromuscular dysfunction.
Today, primary hyperparathyroidism is a different entity. Since the advent of chemical screening
with an autoanalyzer in 1960s, most cases are discovered in asymptomatic patients with
hypercalcemia. Patients may also present with nonspecific complaints of back pain, or they may
have osteopenia, as depicted on radiographic studies. Primary hyperparathyroidism is the most
common cause of hypercalcemia in the outpatient population, second only to malignancy in the
inpatient population. The natural progression of disease in asymptomatic patients is unclear.
Pathophysiology:
Normal parathyroid glands function to maintain appropriate serum calcium concentrations and to
regulate bone metabolism by means of the production of parathyroid hormone (PTH). In the
nonpathologic state, PTH secretion increases in response to low serum calcium concentrations and
enhances the synthesis of 1,25-dihydroxyvitamin D. PTH and 1,25-dihydroxyvitamin D act together
to increase calcium reabsorption in the gut and kidney and to promote osteoclastic resorption and
the demineralization of bone.

Primary hyperparathyroidism is caused by an overproduction of PTH, in excess of the amount

required by the body. In contrast, secondary hyperparathyroidism involves an increase in PTH
levels to meet some bodily requirement. In 75-80% of cases of primary hyperparathyroidism, one or
more adenomas account for the overproduction, whereas approximately 20% of cases are secondary
to diffuse hyperplasia of all glands. Carcinoma accounts for less than 2% of all cases.
The effects of hyperparathyroidism on bone are numerous. Excess PTH results in an increase in
bone breakdown by means of osteoclastic resorption with subsequent fibrous replacement and
reactive osteoblastic activity. The bone may have microfractures, with subsequent hemorrhage and
growth of fibrous tissue and an influx of macrophages. The resulting mass is called a brown tumor
because of the brown color of the vascular elements and blood in the mass. The process of bone
resorption and fibrous replacement results in the characteristic radiologic features of generalized
bone demineralization, resorption, cysts, brown tumors, erosion of the dental lamina dura, and
pathologic fractures.
Other effects of hypercalcemia include nephrolithiasis or nephrocalcinosis, neurologic changes,
peptic ulcer disease, and pancreatitis.
Mortality/Morbidity: Evidence supports an increase in the morbidity and mortality rates in
patients with hyperparathyroidism that is primarily related to cardiac disease. The topic is
controversial, with the results of more recent studies refuting the increased risk. Differences in
mortality data may reflect the different clinical profiles of classic primary hyperparathyroidism and
the modern asymptomatic cohort of patients.
Sex: Incidence of primary hyperparathyroidism in women is 2-3 times the incidence in men.
Age: The average patient age at diagnosis is 55 years. . The incidence peaks in those aged 40-70
years. . The disease is rare in children.
Classification due to etiology.
1. Primary (due to parathyroid glands):
- adenoma of a single gland (80 %), multiple adenomata (5 %);
- hyperplasia of parathyroid glands (15 %);
- carcinoma of a gland (< 5 %);
- associated with syndromes of familial endocrine neoplasia (MEN-types I and II).
2. Secondary (due to increased physiological demand of hormone in response to low serum
Ca in chronic renal failure, malabsorption, rickets and osteomalacia):
- renal;
- intestinal;
- vitamin D insufficiency.
3.
Tertiary (due to development of parathyroid tumor against a background of prolonged
secondary hyperparathyroidism).
Clinical forms of hyperparathyroidism.
1. Bone:
- osteoporosis;
- osteodystrofya.
2. Visceropatic:
- dyspeptic;
- gastrointestinal;
- nephrotic;
- pancreatic.
3. Mixed:
- myopathy;
- mixed damaging of organs and systems

Clinical presentation.
Many patients with mild hypercalcemia are asymptomatic, and the condition is discovered
accidentally during routine laboratory screening.
Onset is usually gradual with bone pain or swelling, rarely sudden with fracture or renal colic.
The clinical manifestations of hypercalcemia include constipation, anorexia, nausea, vomiting with
abdominal pain and ileus, weight loss.. More severe elevation of serum calcium is associated with
emotional lability, confusion, delirium, psychosis, stupor and coma. Myopathy may cause
prominent skeletal muscle weakness. Seizures are rare.
Reversible impairment of the renal concentrating mechanism leads to polyuria, nocturia and
polydipsia. Hypercalciuria with nephrolithiasis (Video) or urolithiasis is common (is noted in 50 %
of patients). Less often, prolonged and severe hypercalcemia may produce reversible acute renal
failure or irreversible renal damage, due to precipitation of Ca salts within the kidney parenchyma
(nephrocalcinosis). Renal damage may result in azotemia and hypertension.
Peptic ulcers and pancreatitis may also be associated with hyperparathyroidism.
Hyperparathyroidism is a disease of increased bone resorption and bone formation. Subsequently,
plain radiographic findings may include resorption and sclerosis and numerous sites n the skeletal
system. Historically, osteitis fibrosa cystica was used to describe the advanced skeletal disease in
primary hyperparathyroidism.
Osteitis fibrosa cystica, in which increased osteoclastic activity causes rarefying osteitis with
fibrous degeneration, the formation of cysts, and the development of fibrous nodules in the affected
bone, may develop in patients severe hyperparathyroidism. Other bony manifestations include bone
pain, tenderness, fracture, deformity, swelling of mandible due to cyst formation (rarely), falling of
teeth.
Cardiovascular disorders are presented as hypertension, arrhythmia, left ventricle hypertrophy.
Investigations.
1. Increased level of serum Ca.
2. A low serum phosphate level.
3. Elevated serum parathyroid hormone.
4. Increased alkaline phosphatase.
5. Hypercalciuria, hyperphosphaturia.
6. X-ray: cortical erosions most marked in phalanges especially radial side of middle phalanx;
destructive bone lesions; Ca deposition on kidney.
Ultrasound and CT scan: localizing of the parathyroid tumor.
Technetium-99m imaging has a sensitivity of 70-95% in depicting parathyroid tumors, and it allows
3-dimensional imaging with anterior-to-posterior localization of the tumor. Studies reveal equal
sensitivities of technetium-99m sestamibi imaging and MRI in the localization of abnormal glands
prior to repeat surgery, with sensitivities of 82-85%. By combining the 2 modalities, the sensitivity
increases to 94%.
Differential diagnosis.
Polyarthritis, radiculitis, tumors of the bones, diabetes insipidus and others.
Treatment.
1. Surgery. It is indicated if the disease is symptomatic or progressive. Chances of cure depend on
successful removal of all excess functioning tissue and on reversibility of renal damage; renal
insufficiency may progress despite cure of the underlying disease. Abnormally functioning
parathyroid glands may be found in unusual locations and experience is required to find them.
Preoperative localization of abnormally functioning parathyroid tissue is possible by immunoassay
of the thyroid venous drainage. When hyperparathyroidism is mild, no special postoperative
precautions are required. In patients with severe osteitis fibrosa cystica, prolonged symptomatic

hypocalcemia may occur and require large doses of Ca together with vitamin D, usually for 1 to 3
month.
2. Conservative treatment include (may be used in patients with hypercacemic crisis, which is
medical emergency and characterized by dehydration, hypotension, abdominal pain, vomiting, fever
and altered consciousness):
- rehydration 2 6 l of sodium chloride solution and furosemid 40 160 mg;
- calcitonine 1 4 units/kg;
- prednisolone 40 60 mg/day.