Pathophysiology of the pituitary and adrenal

glands

The State Education Institution of Higher Professional Training The First Sechenov Moscow State Medical University

under Ministry of Health of the Russian Federation

Lecture presentation

Professor Pirozhkov S.V.

 Department of Pathophysiology

2014-2015 education year

Classification of disorders of the endocrine system (based on the location of disorder)

■ Disorders of the central regulation of the endocrine function due to defects of the hypothalamus (tertiary) or pituitary (secondary)

■ Disorders of the peripheral endocrine glands (primary)

■ Extraglandular disorders:

- abnormal transport of hormones;

- resistance to the effects of hormones;

- abnormal metabolism of hormones

Etiology of hypopituitarismEtiology of hypopituitarism

●● pituitary adenomapituitary adenoma●● pituitary surgery or irradiationpituitary surgery or irradiation●● closed head trauma, hematomaclosed head trauma, hematoma●● infarction during the postpartum period infarction during the postpartum period (Sheehan’s (Sheehan’s

syndrome)syndrome)

●● lymphocytic hypophysitis and other types of lymphocytic hypophysitis and other types of inflammation inflammation

●● hypothalamic or pituitary stalk damage hypothalamic or pituitary stalk damage (sarcoidosis, metastatic carcinoma, germinoma etc.)(sarcoidosis, metastatic carcinoma, germinoma etc.)

● ● ““functional” hypopituitarism functional” hypopituitarism (anorexia nervosa, severe (anorexia nervosa, severe stress)stress)

● ● congenitalcongenital malformation of the malformation of the pituitary/abnormal synthesis of the pituitary pituitary/abnormal synthesis of the pituitary hormoneshormones

The major manifestations of the Sheehan syndrome

Pituitary necrosis

Pallor (decrease of MSH)

Hypothyroidism

Failure of lactation(decrease of prolactin)

Adrenal insufficiency(decrease of ACTH)

Ovarian failure with amenorrhea (decrease of LH, FSH)

Common syndromes of partial hypopituitarism

Deficit of somatotropin Deficit of somatotropin pituitarypituitary nanismnanism

Deficit of TSHDeficit of TSH pituitary hypothyroidismhypothyroidism

Deficit of gonadotropins Deficit of gonadotropins pituitarypituitary hypogonadismhypogonadism

DeficitDeficit ofof ββ––lipotropinlipotropin pituitary pituitary obesityobesity

Deficit of ACTHDeficit of ACTH chr. secondary adrenal insuff.

Etiology of the pituitary hormones excessEtiology of the pituitary hormones excess

● ● AdenomasAdenomas of uncertain provinance of of uncertain provinance of pituitary or, rarely, of hypothalamuspituitary or, rarely, of hypothalamus

● ● Decreased inhibitory action of Decreased inhibitory action of hypothalamus hypothalamus (injury to pituitary stalk)(injury to pituitary stalk)

● ● Extraglandular production of hormones Extraglandular production of hormones (secretion of ACTH or GHRH by malignant (secretion of ACTH or GHRH by malignant tumors)tumors)

Common syndromes produced by pituitary tumorsCommon syndromes produced by pituitary tumors

Prolactin-secreting tumorsProlactin-secreting tumors galactorrheagalactorrhea and/or hypogonadismand/or hypogonadism

GH-secreting tumors GH-secreting tumors gigantism orgigantism or acromegalyacromegaly

ACTH-secreting tumor ACTH-secreting tumor Cushing’s diseaseCushing’s disease

TSH-secreting tumor hyperthyroidism

Large pituitary tumors partial or complete hypopituitarism, visual field and other neurologic disturbances

Somatotropic adenoma of pituitary

C l i n i c a l m a n i f e s t a t i o n s o f a c r o m e g a l y

Thickened calvaria

Acromegalic facies

GoiterHyperostosis (thoracic vertebrae)

Cardiomegaly (hypertension)

Barrel chest

Abnormal glucose tolerance

Male sexual disfunction

Increased size (hand, feet)

Degenerative arthritis

Peripheral neuropathy

Thickened skin (hypertrophy of sebaceous and sweat glands)

Lesions:● Idiopathic Sporadic mutations Familial (30%)● Tumors● Trauma● Post-hypophysectomy (20%)● Other

Collecting duct

Neurohypophysis

Decreased renal water reabsorption

Diabetes insipidus

Adenohypophysis

ADH Deficiency

Urine

Inappropriately dilute urine

Impairment of water reabsorption

P a t h o g e n e s i s o f t h e ADH d e f i c i e n c y

The syndrome of inappropriate ADH The syndrome of inappropriate ADH secretion (SIADH)secretion (SIADH)

Causes:● Drug- or disease-induced release of ADH from

the neurohypophysis - central nervous system disorders (head trauma,

subdural hematoma, brain tumor, cerebral atrophy, acute encephalitis)

- drugs that release or potentiate the action of ADH (cytostatics, general anesthetics, tricyclic antidepressants)

● Ectopic ADH production and release - from neoplastic tissue (small cell carcinoma of lungs,

pancreatic carcinoma, lymphoma, thymoma etc.)

CAUSES OF THE ADRENAL CORTEX CAUSES OF THE ADRENAL CORTEX HYPOFUNCTIONHYPOFUNCTION

Primary – inability of the adrenals to elaborate sufficient quantities of hormone

Secondary – low production of adrenal hormones due to inadequate ACTH formation or release

Etiology of the primary chronic adrenocortical Etiology of the primary chronic adrenocortical insufficiencyinsufficiency (Addison’s disease)(Addison’s disease)

► Idiopathic atrophy (autoimmune)

► Chronic granulomatous diseases: tuberculosis, histoplasmosis, criptococcosis

► Bilateral hemorrhage

► Tumor metastases

► Amyloidosis of adrenals

► Adrenomyeloneuropathy

► Sarcoidosis of adrenals

► Familial adrenal insufficiency

CLINICAL SIGNS AND SYMPTOMS OF CHRONIC CLINICAL SIGNS AND SYMPTOMS OF CHRONIC ADRENOCORTICAL INSUFFICIENCYADRENOCORTICAL INSUFFICIENCY (Addison’s disease)(Addison’s disease)

Insidious onset of:

● fatigability, weakness

● anorexia, nausea, vomiting

● diarrhea, abdominal pain

● weight loss

● cutaneous and mucosal pigmentation

● arterial hypotension

● occasionally - hypoglycemia

● excessive irritability, restlessness

HYPERFUNCTION OF THE ADRENAL CORTEX

Excess of hyperaldosteronism

aldosterone

Excess of Cushing’s cortisol syndrome/disease

Excess of adrenal virilism androgens

SIGNS AND SYMPTOMS OF PRIMARY SIGNS AND SYMPTOMS OF PRIMARY HYPERALDOSTERONISM HYPERALDOSTERONISM (Conn’s syndrome)(Conn’s syndrome)

◘ Hypersecretion of aldosterone that is not suppressed appropriately in response to volume expansion (salt loading)

◘ Low plasma renin activity

◘ Hypernatremia, hypokalemia

◘ Nonrespiratory excretory alkalosis

◘ Diastolic arterial hypertension

◘ Headaches

◘ Muscle weakness, fatigue

◘ Polyuria (at advanced stages)

◘ ECG: arrhythmia, the presence of U-wave

ETIOLOGY OF THE HYPERCORTISOLISMETIOLOGY OF THE HYPERCORTISOLISM

CUSHING’S - excessive production DISEASE of ACTH (secondary form) or CRF (tertiary form)

CUSHING’S - excessive production SYNDROME of cortisol in the adrenal glands (primary form)

THE MAIN SYMPTOMS OF CUSHUNG’S DISEASE OR SYNDROME

Emotional disturbanceEnlarged sella turcica

Moon face

OsteoporosisCardiac hypertrophy

Buffalo humpObesity

Adrenal tumor or hyperplasia

Thin, wrinkled skin

Abdominal striaeAmenorrheaMuscle weaknessPurpura

Skin ulcers(poor wound healing)