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  Department of Pathophysiology Pathophysiology of the pituitary and adrenal glands Lecture presentation Professor Pirozhkov S.V. 2015-2016 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

● pituitary surgery or irradiation ● closed head trauma, hematoma Etiology of hypopituitarism ● pituitary adenoma ● pituitary surgery or irradiation ● closed head trauma, hematoma ● infarction during the postpartum period (Sheehan’s syndrome) ● lymphocytic hypophysitis and other types of inflammation ● hypothalamic or pituitary stalk damage (sarcoidosis, metastatic carcinoma, germinoma etc.) ● “functional” hypopituitarism (anorexia nervosa, severe stress) ● congenital malformation of the pituitary/abnormal synthesis of the pituitary hormones

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) The major manifestations of the Sheehan syndrome

Common syndromes of partial hypopituitarism Deficit of somatotropin pituitary nanism Deficit of TSH pituitary hypothyroidism Deficit of gonadotropins pituitary hypogonadism Deficit of β–lipotropin pituitary obesity Deficit of ACTH chr. secondary adrenal insuff.

Etiology of the pituitary hormones excess ● Adenomas of uncertain provinance of pituitary or, rarely, of hypothalamus ● Decreased inhibitory action of hypothalamus (injury to pituitary stalk) ● Extraglandular production of hormones (secretion of ACTH or GHRH by malignant tumors)

Common syndromes produced by pituitary tumors Prolactin-secreting tumors galactorrhea and/or hypogonadism GH-secreting tumors gigantism or acromegaly ACTH-secreting tumor Cushing’s disease TSH-secreting tumor hyperthyroidism Large pituitary tumors partial or complete hypopituitarism, visual field and other neurologic disturbances

Thickened calvaria Somatotropic adenoma of pituitary Acromegalic facies Goiter Hyperostosis (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) 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

Impairment of water reabsorption Decreased renal water reabsorption Neurohypophysis Adenohypophysis Lesions: ● Idiopathic Sporadic mutations Familial (30%) ● Tumors ● Trauma ● Post-hypophysectomy (20%) ● Other ADH Deficiency Impairment of water reabsorption Collecting duct Urine Decreased renal water reabsorption Inappropriately dilute urine Diabetes insipidus 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

CAUSES OF THE ADRENAL CORTEX HYPOFUNCTION 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 insufficiency (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

● anorexia, nausea, vomiting ● diarrhea, abdominal pain ● weight loss CLINICAL SIGNS AND SYMPTOMS OF CHRONIC ADRENOCORTICAL INSUFFICIENCY (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 HYPERALDOSTERONISM (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 HYPERCORTISOLISM CUSHING’S - excessive production DISEASE of ACTH (secondary form) or CRF (tertiary form) SYNDROME of cortisol in the adrenal glands (primary form)

THE MAIN SYMPTOMS OF CUSHUNG’S DISEASE OR SYNDROME Emotional disturbance Enlarged sella turcica Moon face Osteoporosis Cardiac hypertrophy Buffalo hump Obesity Adrenal tumor or hyperplasia Thin, wrinkled skin Abdominal striae Amenorrhea Muscle weakness Purpura Skin ulcers (poor wound healing)