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PATHOLOGY
Presented by
Voltaire C. Yabut, M.D. DPSP
PITUITARY GLAND
- A pea-sized gland, weighs 0.5 gm & measures 1cm, attached
to the hypothalamus by a stalk
- Two lobes: anteroir & posterior
- Anterior lobe (adenohypophysis)
- derived from Rathke’s pouch
- contains cells that secrete trophic hormones that activate
peripheral endocrine glands
- hypothalamic releasing hormones are delivered via a
portal venous system
PITUITARY GLAND (CONT.)
- Posterior lobe (neurohypophysis)
- derived from outpouching from floor of 3rd ventricle
- has a separate blood supply
- consists of modified glial cells & axons extending from the
supraoptic & paraventricular nuclei in the hypothalamus
- neurons in the supraoptic & paraventricular nuclei produce
ADH & oxytocin
- ADH & oxytocin are stored in axon terminals in the post.
lobe
THE ADENOHYPOPHYSIS
- Five cell types in the adenohypophysis by immunostaining:
1- Lactotrophs (Mammotrophs): Prolactin (Prl) - acidophils.
2- Somatotrophs: growth hormone (GH) - acidophils.
3- Corticotrophs: proopiomelanocortin (POMC) precursor for
adrenocorticotropic hormone (ACTH), melanocyte
stimulating hormone (MSH), β-endorphin, and β-lipotropin
- basophils.
4- Thyrotrophs: thyroid stimulating hormone (TSH) - basophils.
5- Gonadotrophs: follicle stimulating hormone (FSH) &
luteinizing hormone (LH) - basophils.
Hypothalamic Releasing Corresponding Anterior
Hormone Pituitary Hormone(s)
Gonadotropin Releasing Luteinizing Hormone (LH)
Hormone (GnRH) Follicular Stimulating
Hormone (FSH)
1. Prolactinomas (Prl)
2. Somatotroph (GH) adenomas
3. Corticotroph (ACTH) adenomas
Acromegaly;
- adult onset excess growth hormone (GH) ⇒ enlargement of the
skull, facial bones, jaw, hands, feet, soft tissues & organs.
- diabetes, hypertension, muscle weakness, arthritis,
gonadal dysfunction, cardiovascular disease
Gigantism;
- GH excess occurs in children (before closure of epiphyses).
- generalized increase in body size
- disproportionately long arms and legs
ACTH Secreting
Pituitary Adenoma – +
Cortisol Secreting
Adrenocortical Neoplasm – –
ACTH Secreting
Nonendocrine Neoplasm – –
–– = does not suppress
+ = does suppress
OTHER FUNCTIONING ADENOMAS
- Gonadotroph adenomas:
- majority produce FSH, some FSH & LH, rarely only LH
- MC occur in middle-aged men & women
- usually are macroadenomas
- symptoms MC related only to local mass effects
- may cause amenorrhea or galactorrhea, ⇓ libido in men
- Embryology:
- the thyroid develops from the primitive pharynx
- the developing thyroid is attached to the base of the tongue by the
thyroglossal duct
- the thyroid descends in the midline & assumes its final position
in the anterior neck below the larynx
- excessive descent gives rise to a substernal thyroid & incomplete
descent ⇒ ectopic thyroid higher in the neck or tongue
- persistence of remnants of the thyroglossal duct can ⇒
thyroglossal duct cyst
Physiologic Effects of
Thyroid Hormones
• ⇑ gluconeogenesis, glycogenolysis,
lipolysis & ATPase’s
• ⇒ ⇑ basal metabolic rate & heat
production
• ⇑ protein catabolism
• ⇒ muscle wasting, osteoporosis
• ⇑ sympathetic activity
• ⇒ tachycardia & arrythmias
HYPERTHYROIDISM
= a hypermetabolic state, caused by increased levels of
circulating T3 & T4.
Effects: nervousness, warm moist skin, fine tremors,
palpitations, rapid pulse, exophthalmos, weight loss, heat
intolerance, muscle atrophy & weakness, osteoporosis
Most Common Causes: Graves’ disease, toxic
multinodular goiter, toxic adenoma
Less Common Causes:
- thyroiditis, struma ovarii, toxic carcinoma
- TSH-secreting pituitary adenoma
- overtreatment with thyroid hormone tablets (factitious
hyperthyroidism)
HYPOTHYROIDISM
= a hypometabolic state caused by deficiency of T3 & T4.
Cretinism (congenital hypothyroidism)
- Clinical:
- severe mental retardation
- short stature
- coarse facial features, protruding tongue
- Causes:
- Endemic - due to dietary iodine deficiency
- Sporadic
- thyroid dysgenesis
- inherited defects in thyroid hormone synthesis
- inherited peripheral tissue resistance to thyroid hormone
HYPOTHYROIDISM (cont.)
Clinical:
- MCC of hyperthyroidism, peak incidence 20-40 yrs. of age
- a disease of females (F/M 10:1), affects 1-2% of women in US
- hyperthyroidism, symmetrical thyroid enlargement
- opthalmopathy and dermopathy (pretibial myxedema)
- familial predisposition, associated with HLA-B8 & HLA-DR3
- Laboratory values: ⇑ T3 & T4, ⇓ TSH and ⇑ radioactive iodine
uptake
GRAVES’ DISEASE (cont.)
Pathogenesis:
- An abnormality in T-suppressor cells ⇒ T-helper cells that
react to thyroid Ag’s ⇒ elaboration of B-cell clones capable of
producing autoantibodies reactive with TSH receptors.
- IgG antibodies directed against TSH receptors, act as agonists
⇒ ⇑ thyroid hormone secretion.
- The autoantibodies were originally called long acting thyroid
stimulator (LATS), because the peak secretion of thyroid
hormone occurs 16 hours after the exposure of thyroid tissue to
antibody, compared with 2 hours for TSH.
Therapy:
− β-blockers, propylthiouracil, potassium iodide, radioiodine
ablation, surgery
GOITER
- sporadic
- goitrogens
- hereditary defect in thyroid hormone synthesis
- Clinical: most patients are euthyroid
MULTINODULAR GOITER
= nodular enlargement, derived from diffuse goiter
- both monoclonal & polyclonal nodules (adenomatous goiter)
Clinical:
- most patients are euthyroid
- mass effects: compression of trachea, vessels & nerves, & dysphagia
- hyperthyroidism (toxic multinodular goiter)
- due to a hyperfunctioning nodule
- not accompanied by opthalmopathy or dermopathy
Morphology:
- hyperplasia of all (4) parathyroid glands
- skeletal changes of “renal osteodystrophy”
- metastatic calcification
Testosterone:
- Excess testosterone in females causes defemenization &
virilization; (hirsutism, acne, amenorrhea, clitoral enlargement,
atrophy of the breasts & uterus, deepening of the voice & frontal
balding).
- In boys, excess testosterone leads to precocious puberty.
DISEASES OF ADRENAL CORTEX
Hyperfunction (hyperadrenalism):
- Cushing’s syndrome
- Hyperaldosteronism
- Adrenogenital syndromes
Hypofunction (hypoadrenalism):
- Acute (e.g. Waterhouse-Friderichsen Syndrome)
- Chronic:
- primary (due to adrenal cortical insufficiency, e.g.
Addison’s
disease)
- secondary (due to ACTH deficiency)
- tertiary (rarely - due to hypothalamic CRH deficiency).
CUSHING’S SYNDROME
Etiology:
1- Exogenous: high dose cortisone therapy (MCC).
2- Pituitary hypersecretion of ACTH (Cushing’s disease),
accounts for 70% of endogenous hypercortisolism.
Associated with hyperpigmentation of the skin (↑ MSH).
3- Autonomous hypersecretion of cortisol by an adrenal
adenoma, carcinoma or primary hyperplasia (i.e. ACTH
independent).
4- Ectopic production of ACTH or CRH by nonendocrine
neoplasms (bronchogenic small cell carcinoma).
CUSHING’S SYNDROME (cont.)
Clinical features: truncal obesity, moon face, hirsutism,
cutaneous striae, muscle weakness, osteoporosis,
hypertension & hyperglycemia
Changes are reversible if the cause is corrected.
Morphology:
• Cushing’s disease: ACTH is elevated ⇒ adrenals are
bilaterally hyperplastic. Changes are the same with ectopic
ACTH or CRH.
• Adrenocortical neoplasms: uninvolved adrenal cortex is
usually atrophic due to ACTH suppression.
• Adenomas are small & cytologically bland appearing
• Carcinomas are large & often anaplastic
Diagnosis:
24 hr urine free cortisol, plasma ACTH, Dexamethasone
Suppression Test
PRIMARY HYPERALDOSTERONISM
= excessive secretion of aldosterone independent of renin-
angiotensin system.
Features: hypervolemia, hypokalemia, hypertension, low renin
Causes:
- MCC is aldosterone-secreting adenoma (Conn’s syndrome) in
80% of cases
- Bilateral idiopathic hyperplasia (? due to an abnormal
secretagogue)
- Glucorticoid-suppressible hyperaldosteronism: hybrid cells
produce both cortisol & aldosterone, ⇑ aldosterone under
influence of ACTH, suppressible by administration of
dexamethasone
Prognosis: adenomas are curable by surgery.
ADRENOGENITAL SYNDROMES