Endocrine & Metabolic Physiology

 Laboratory findings in Cushing's syndrome:
1.  Urinary free cortisol excretion increases (normal < 100ug/day).
2.  Plasma cortisol increases (normal 10ug/dl, average).
3.  Dexamethasone suppression test (DST).
Here synthetic steroid (dexamethasone) is given which is expected to reduce ACTH and cortisol secretion by negative feedback. Normally plasma cortisol decreases, but failure of plasma cortisol reduction following DST suggests Cushing's syndrome.
4. Plasma ACTH (normal = 9.52 pg/L)
Moderately increaed in Cushing's disease, markedly increased in ectopic ACTH and very low or undetectable in adrenal tumor.

Steroid & thyroid hormones arr lipophilic

Reference: Ganong 26^th; Figure-2.21

Hypothalamus contains neurosecretory cells.

Primary hyperparathyroidism (PHP)

 Definition: It is the hypercalcemic disorder due to excessive secretion of PTH.

Causes:
1. Parathyroid adenoma (80 %).

2. Primary hyperplasia of parathyroid gland (15 %). 3.Parathyroid carcinoma.

TSH works on iodide trapping

Prognathism is a feature of acromegaly

Receptors of calcitonin are found in bone & kidney.

Others are classical sites of insulin receptor.

Effects of insulin on various tissues
Adipose tissue
Increased glucose entry Increased fatty acid
Increased glycerol phosphate synthesis Increased triglyceride deposition Activation of lipoprotein lipase Inhibition of hormone sensitive lipase Increased K+ uptake
Muscle
Increased glucose entry Increased glycogen synthesis Increased amino acid uptake
Increased protein synthesis in ribosomes Decreased protein catabolism
Decreased release of gluconeogenic amino acids Increased ketone uptake
Increased K+ uptake

Leptin produces satiety

Circulating level of Leptin is responsible for food intake regulation. Leptin decreases food intake.
Reference-Ganong/26th/P-481/Figure-26.9

Testosterone, the principal hormone of the testes, is a C19 steroid with a hydroxyl group in the 17 position . It is synthesized from cholesterol in the Leydig cells and is also formed from androstenedione secreted by the adrenal cortex. 

Pituitary apoplexy ( characterized by a sudden headache, vomiting,visual disturbances and hormonal dysfunction. The cause is most commonly
due to the abrupt growth of a pituitary adenoma or pituitary infarction.The headache in apoplexy is usually very abrupt and can be mistaken for
a subarachnoid haemorrhage, although usually not as severe. Thepresentation can be unilateral or generalized. Visual defects are most
commonly of the superior quadrant bitemporally. Visual disturbances,such as loss of vision and opthalmoplegia affecting cranial nerves III, IV
and VI, help differentiate apoplexy from other intracranial pathology.Hypopituitarism can also follow an apoplexy although this is dependent
on degree of damage and often patients present feeling very tired ornauseous. Kallman syndrome (A) is characterized by gonadotrophin
deficiency and congenital anosmia. Septo-optic dysplasia (B) is a congenitaldisorder characterized by the triad of optic nerve hypoplasia, hypopituitarism
and forebrain abnormalities. The empty sella syndrome (D) is theobservation of absent pituitary tissue within the sella turcica observed on
imaging, however pituitary function is normal due to ectopic or unusual position of pituitary tissue within the sella fossa. Sheehan syndrome (C) is
also called postpartum hypopituitarism and is most commonly a rare complication of pregnancy. Patient's present with agalactorrhoea,
amenorrhoea and hypothyroidism after pregnancy.

The kidneys synthesize glucose from amino acids and other precursors during prolonged fasting, a process referred to as gluconeogenesis. The kidneys’ capacity to add glucose to the blood during prolonged periods of fasting rivals that of the liver.

Primary (ACTH) Addison's disease Common causes
·       Autoimmune
o   Sporadic
o   Polyglandular syndromes
·       Tuberculosis
·       HIV/AIDS
·       Metastatic carcinoma
·       Bilateral adrenalectomy
Rare causes
·       Lymphoma
·        Intra-adrenal hemorrhage (Waterhouse-Friedrichsen syndrome following meningococcal sepsis)
·       Amyloidosis
·       Haemochromatosis

GH, Glucagon, cortisol etc. are diabetogenic hormones.

Thyroid hormone increase gut motility. So hypothyroid state causes constipation.

Norepinephrine has shortest half-life.

Hypoparathyroidism leads to hypocalcemia, by decreasing the resorption of calcium from bones. Hypocalcemia causes neuromuscular hyperexcitability, resulting in hypocalcemic tetany. Normally, tetany occurs when plasma calcium level falls below 6 mg/dL from its normal value of 9.4 mg/dL.

Hypokalemia occurs in Conn's syndrome

Aldosterone is produced in the zona glomerulosa of the adrenal cortex because that layer contains the enzyme for conversion of corticosterone to aldosterone (aldosterone synthase). Cortisol is produced in the zona fasciculata. Androstenedione and dehydroepiandrosterone are produced in the zona reticularis. Testosterone is produced in the testes, not in the adrenal cortex.

Insulin is major anabolic hormone of the body

With renin high and aldosterone high (secondary hyperaldosteronism)
• Inadequate renal perfusion, e.g. diuretic therapy, cardiac failure, liver failure, nephrotic syndrome, renal artery stenosis.
• Renin-secreting renal tumor (very rare)

Thyroid hormone, an amine, acts on its target tissues by a steroid hormone mechanism, inducing the synthesis of new proteins. The action of antidiuretic hormone (ADH) on the collecting duct (V2 receptors) is mediated by cyclic adenosine monophosphate (cAMP), although the other action of ADH (vascular smooth muscle, V1 receptors) is mediated by inositol 1,4,5-triphosphate (IP3). Parathyroid hormone (PTH), β1-agonists, and glucagon all act through cAMP mechanisms of action.

Explanation-
★Thyroid-stimulating hormone (TSH) is secreted by the anterior pituitary. Dopamine, growth hormone–releasing hormone (GHRH), somatostatin, and gonadotropin-releasing hormone (GnRH) all are secreted by the hypothalamus. Oxytocin is secreted by the posterior pituitary. Testosterone is secreted by the testes.
Reference-Guyton & Hall/13rd/P-927 & BRS physiology/6th/P-233/T-7.1

Oxytocin is secreted from posterior pituitary.

Glucocorticoid secretion unaffected
-High potassium intake
-Low sodium intake
-Constriction of inferior vena cava in thorax
-Standing
-Secondary hyperaldosteronism (In some cases of congestive heart failure, cirrhosis, and nephrotic syndrome)

According to the NIH, the following desired values are used to measure an overall lipid profile:

LDL: Less than 160 mg/dL (if you have heart disease or diabetes, less than 100 mg/dL)
HDL: Greater than 40–60 mg/dL
Triglycerides: 10–150 mg/dL