Endocrine Flashcards Preview

initially medications but surgery may be needed

occurs due to GH excess after fusion of the epiphysis (gigantism occurs due to GH excess occurring before epiphyseal fusion)

• almost always due to adenoma (v. rarely ectopic GHRH )

Acromeg

Measure GH and IGF-1(Insulin-like growth factor-1):

GH acts on liver to produce IGF-1. IGF-1 level is more stable than GH and therefore more important in diagnosis of acromegaly.

GTT with GH measurement:

In normal individuals, GH levels fall following oral glucose, and at least one of the samples during the test should have undetectable GH levels. Failure of suppression or a paradoxical rise in GH suggests acromegaly.

• Surgical

• Medical

• Radiotherapy

1. Antidiuretic hormone (ADH)

2. Oxytocin

• ADH is clinically important. It's deficiency cause diabetes insipidus (DI).

• In appropriate secretion of ADH causes the syndrome of inappropriate ADH secretion (SIADH)

decreased blood volume and raised plasma osmolality.

ADH causes water retention by increasing permeability in the distal convoluted tubules and collecting ducts in the kidney. ADH will tend therefore to restore blood volume and normalize plasma osmolality. The action of ADH will cause a decrease in urine volume and increased urinary osmolality.

caused by absolute deficiency of ADH: – genetic

– hypothalamic or high pituitary stalk lesion

– idiopathic

caused by resistance to ADH action – genetic

– metabolic: hypokalemia, hypercalcemia

– Drugs: Lithium

• Fluid restriction for 8 hours

• Ask the patient to pass urine and discard it.

• Weigh patient at start of test; continue weighing at 1-hour intervals

• Measure serum and urine osmolality, urine volume and weight hourly for up to 8 hours..

• Stop test after 8 hours or if patient’s weight is <5% off his initial weight.

• If results suggest DI, give Desmopressin:

– Measure plasma osmolality, urine volume and

osmolality

295 mosm/kg and the urine osmolality exceeds 600 mosm/kg at some time during the test.

inappropriate secretion of ADH i.e. ADH secretion which continues despite lack of physiological stimuli.

SIADH

– Post-operative

– Intra-cranial disease: encephalitis, meningitis, head injury

– Neoplasms: eg small cell carcinoma of the lung

– Pulmonary disease: pneumonia, tuberculosis

– Drugs/Medications

Thyroxine (T4) and tri-iodothyronine (T3)

• 85% of T3 is produced peripherally, by conversion from T4.

C cells

• Essential for normal growth and development

catabolic functions 

• Stimulate basal metabolic rate

• Increase the sensitivity of the cardiovascular and nervous system to catecholamines

• Weight loss

• palpitations, tachycardia,

• proximal myopathy

• Diarrhea

atrial fibrillation • • sweating, heat intolerance, •

fatigue

• generalized muscle weakness,

Lid-lag

Exophthalmos

• Goiter

• Menstrual disorders and infertility

• Effects on heart (arrhythmias) and bone

(osteoporosis)

toxicity caused by excess thyroid hormones, which may be due to a hyperactive thyroid gland; it may be due to exogenous

thyroid hormones

Grave’s disease: the most common cause:

toxic adenoma

 toxic multinodular goiter

 thyroiditis

 Functional thyroid cancer (produces thyroid hormones)

– is an autoimmune disease with HLA associations

– Causes goiter with diffuse enlargement

– Characterized by ophthalmopathy and pretibial myxedema

– thyroid stimulating immunoglobulins which bind TSH receptors

– Subacute (De Quervain’s) thyroiditis: pain, tenderness, fever

– Postpartum thyroiditis due to natural immunosupression during pregnancy

• Lethargy, tiredness

• Cold intolerance

• dryness of skin and hair

• Hoarseness

• Weight gain

• slow relaxation of tendon reflexes

• Psychosis

• Carpal tunnel syndrome • Angina, bradycardia

• Menstrual disturbances • galactorrhea, infertility • Generalized myxedema • Hyperprolactinemia

Chronic autoimmune thyroid disease (Hashimoto’s disease)

Post-surgery,antithyroiddrugsorradioactiveiodine

Congenital hypothyroidism

• Iodinedeficiency

• Pituitary or hypothalamic disease (secondary hypothyroidism)

lymphocytic infiltration, goiter, autoantibodies, HLA association

is inadequate thyroid hormone production

in newborn infants, because of:

– an anatomic defect in the gland

– Dyshormonogenesis: deficiency of the enzyme that makes thyroid hormones

– iodine deficiency

• TSH measurement: may be used in Screening alone or with measurement of FT4 and FT3.

• You need to measure TSH and FT4 to determine the state of thyroid function (hyper-, hypo-, or euthyroid)

• Thyroidautoantibodies:

– antimicrosomal and antithyroglobulin antibodies are present in

high titres in Hashimoto’s disease

– Thyroid stimulating immunoglobulins (TSI) occur in Grave’s disease

• TRHtest(notcommonlyused)

• Thyroid isotope scan (not commonly used)

• Fine-needle aspiration (in diagnosis of thyroid cancer)

is any visible enlargement of the thyroid gland.

• A goiter may be associated with hyper-, hypo- or euthyroid state

• Agoitermayproducemasseffects

• Typesofgoiter:

– Simple diffuse goiter

– Simple multinodular goiter – solitary thyroid nodule

Abnormal TFTs in severe illness

• (TFTs =Thyroid function tests ie TSH, FT4 and FT3 levels).

– decreased peripheral conversion of T4 to T3

– Abnormality of binding protein

– Effects of circulating inflammatory mediators on metabolism of thyroid hormones

high TSH levels and normal FT4/FT3 levels in an asymptomatic individual

• Can convert to hypothyroidism, specially if anti- thyroid antibodies present

with endothelial dysfunction which may lead to atheroma

Treat when TSH >10 mU/L (Normal below 5 mU/L)

Papillary carcinoma

Mostly are benign

Follicular carcinoma 

• Total Thyroidectomy. This operation is designed to remove all of the thyroid gland. It is the operation of choice for all thyroid cancers.

• Patients receive thyroid hormones to suppress TSH levels.

TSH, Thyroglobulin (levels should be suppressed)

parafollicular cells (also called C cells) of the thyroid; they produce calcitonin

– Sporadic- accounts for 80% of all cases of medullary thyroid

cancer.

– Part of Multiple Endocrine Neoplasia Syndromes (MEN 2A or MEN 2B)

– Inherited medullary carcinoma not associated with endocrine disorders

 total thyroidectomy; Calcitonin measurement is useful in monitoring of treatment

• Zona glomerulosa

– produces mineralocorticoids

• Zona fasiculata

• Zona reticularis

– the two inner layers produce glucocorticoids and

androgens:.

– The adrenal androgs are: dehydroepiandrosterone, androstenedione, testosterone

– small amounts of progestagens and estrogens are also produced

– insulin antagonist

– anti-inflammatory

– has weak mineralocorticosteroid properties

increases sodium reabsorption in the kidney in exchange for potassium and hydrogen ions

Excess can cause precocious puberty in boys and masculinizing effects in women

The adrenal cortex typically produces small amounts; rarely an estrogen-producing tumor produces significant amounts

• 95% of cortisol is protein-bound; mostly to Cortisol-binding globulin (CBG).

• Aldosterone:

– only 60% bound to albumin

• Adrenal androgens and estrogens:

– are transported mainly bound to Sex Hormone

Binding Globulin (SHBG)

LEVELS are related to the amount of binding protein available 

– Level is controlled by ACTH and CRH by the negative feedback mechanism

– circadian rhythm: highest concentration of ACTH and cortisol in the morning and lowest at mid-night

– stress can override the circadian rhythm

 primary stimulator of aldosterone synthesis and secretion is the renin-angiotensin system, which is activated in response to hypotension and sodium loss. Also sympathetic nervous system and high potassium concentrations stimulate aldosterone release

ACTH

Primary Adrencortical insufficiency or Addison’s disease

– autoimmune disease, affecting the adrenal gland alone or in association with other autoimmune diseases eg thyroid disease, premature ovarian failure and type 1 DM

– infections: TB, AIDS, meningitis ( causing Water-house- Fridericksen syndrome), which cause hemorrhage and destruction of the adrenal glands)

– Bilateral secondary carcinoma

pituitary disorders. Not associated with hyperpigmentation or electrolytes disturbances

often precipitated by infection in a patient with adrenocortical insufficiency; characterized by circulatory shock, volume depletion, anorexia, nausea and vomiting

tiredness, weakness, anorexia, apathy, abdominal pain, hyperpigmentation, postural hypotension

pituitary disorders. There is no pigmentation due to absence of ACTH, and initially there are no electrolyte disturbances due to presence of aldosterone.

– Exogenous steroids

– Pituitary dependent

– Adrenal adenoma

– EctopicACTH

Cushings syndrome 

Excludeexogenousglucocorticoids

• Perform one of the following tests to confirm hypercortisolism:

1. 24 hour urinary free cortisol: commonly used screening test

2. 1 mg Overnight DST (Dexamethasone suppression test):

• It involves taking a small dose of a cortisol-like drug called dexamethasone (1 mg) at 11 p.m. and having blood drawn for cortisol the following morning. Normal individuals typically have very low levels of cortisol in these samples (<50 nmol/L), indicating that ACTH secretion is suppressed, while cortisol level is not suppressed in patients with Cushing's disease

3. Late-night salivary cortisol: new test

(i) ACH-producing pituitary tumor (ii) ectopic ACTH production or (iii) adrenal gland tumor:.

8 mg over night DST or two day 8 mg DST PlasmaACTH

Localization: MRI or CT scan

Inferior petrosal sinus sampling: used to identify the source of the ACTH secretion, after diagnosis of Cushing's syndrome has been established (if no adenoma was found by MRI)

Primary hyperaldosteronism or primary aldosteronism

Hyperaldosteronism adenoma (most common)

Aldosterone : renin ratio (ARR)

Confirm test:

Oral sodium loading test

Fludrocortisone suppression test

Ct scan

Adrenal venous sampling for lateralizing the source of excess aldosterone 

C-21 hydroxylase deficiency

Autosomal recessive disorders characterized by partial enzyme deficiency in the synthesis of adrenal steroids

1.

Simple virilizing (non salt-losing CAH):

– Girls: ambiguous genitalia. (often born with an enlarged clitoris and the labia may be partially fused

– Boys: Normal at at birth. Penile enlargement, early pubic hair and rapid growth in height when the child is 4 or 5 years old.

Adrenal crisis (salt-losing CAH): occurs when aldosterone production is affected leading to circulatory collapse, vomiting

late-onset CAH: hirsutism, infertility

Deficiency causes features of androgen excess, including ambiguous genitalia and virilization in females and precocious puberty in male children. Most patients also have hypertension

• Deficiency causes decreased production of glucocorticoids and sex

steroids and increased synthesis of mineralocorticoid precursors.

• Reduced levels of both gonadal and adrenal sex hormones result in ambiguous genitalia in males. In females, there is delayed puberty, absent secondary sexual characteristics, or primary amenorrhea. Excessive mineralocorticoid activity produces varying degrees of hypertension and hypokalemia

diagnosis made by finding of high level of 17  hydroxyprogesterone in blood in a morning sample. In borderline cases, Short synacthen test with measurement of 17  hydroxyprogesterone in blood before and after administration of synacthen

mutational analysis obtained by chorionic villous sampling or amniocentesis.

– Mothers are treated with dexamethasone, which is started early

A tumor of Chromaffin cells.

• Secrets mostly adrenaline and noradrenaline and rarely dopamine 

• 10% extraadrenal; 10% inherited; 10% malignant; 10% bilateral; 10 in childhood;10% component of multiple endocrine neoplasia, MEN2a and MEN2b

• Measure catecholamines and their metabolites in a 24- hour urine collection

• MRI or CT scanning: for localization of tumor

• 123I-metaiodobenzylguanidine(MIBG)scintigraphy:

– MIBG selectively concentrates in APUD system (Amine Precursor Uptake & Decarboxylation system)

– used selectively, such as for the rare patient with a biochemical diagnosis of pheochromocytoma and no tumor seen on exhaustive anatomical imaging.

• Selectivevenoussampling:

– used for patients in whom standard techniques fail to localize the tumour

occurs mostly in the adrenals, occasionally in the sympathetic chain.

Most common product is dopamine and metabolite

homovanillic acid (HVA), but catecholamine's are secreted

blood pH; inonization of calcium

is increased in acidosis and decreased in alkalosis

hypercalcemic hormone; it’s release is regulated by the level of ionized calcium in the blood. It acts on bone to release calcium and on the kidney to increase calcium reabsorption and decrease reabsorption of phosphates and bicarbonates.

• It activates vitamin D in the kidney.

Activated vitamin D acts on the gut to enhance absorption of calcium and phosphates and acts on bone to facilitate bone resorption and release of calcium

probably not involved in the regulation of calcium metabolism

1. Hyperparathyroidism 2. Malignantdisease

• Other causes:

• Excessive vitamin D:-vitamin D intoxication

• Granulomas (tuberculosis, lymphoma, sarcoidosis) because they activate vitamin D

• Highboneturnover – thyrotoxicosis

– Paget’s disease

1. Asymotomatic: One half of patients are asymptomatic

2. Renal

– Polyuria and thirst

– Stones

– Nephrocalcinosis; deposition f calcium crystals in kidney – May lead to renal failure

3. Musculoskeletal

– Muscle weakness

– Rarely demineralization, subperiosteal bone resorption, bone cysts (osteitis fibrosa cystica)

4. Neurological

– Psychiatric/neurological symptoms

5. Gastrointestinal

– Anorexia, constipation and ulcers

mostly solitary adenoma, rarely hyperplasia or carcinoma

 is the reaction of the parathyroid glands to a hypocalcemia caused by something other than a parathyroid pathology

occurs when PTH increases to maintain normocalcemia in the setting of vitamin D deficiency ; eventually parathyroid hyperplasia occurs and PTH secretion becomes independent of calcium level; often seen in patients with chronic renal failure.

multiple endocrine neoplasia (MEN1 and MEN2 syndromes)

Bone mets: Local cytokine secretion or protaglandin producion causes bone destruction 

Humoral hypercalcemia of malignancy- Solid tumors secrete parathyroid hormone 

1,25- dihydroxy vitamin D induced hypercalcemia secondary to lymphomas exrpresss 1 a-hydroxylase 

– Correct dehydartion

– Frusemide

– Biphosphonates

– Calcitonin

• Hypoalbuminemia (will cause a low total plasma calcium but

the ionized calcium level will be normal)

• ChelationbyEDTA

• PTH-related: hypoparathyroidism, pseudohypoparathyroidism, hypomagnesemia

• Defect in vitamin D metabolism: rickets, osteomalacia, Chronic renal failure, vitamin D resistant rickets, liver disease, anticonvulsive therapy

• Acute pancreatitis

increased neuromuscular excitability with tetany, parathesiae and muscle cramps.

• prolonged hypocalcaemia is associated with cataract, mental retardation, psychosis, increased intracranial pressure and seizures.

DiGeorge 

 decreased responsiveness of target organs because of problems with PTH receptors. Sex-linked; males affected twice as often as females

• Reducedabsorption: – Malabsorption

• Increasedcellular uptake:

– treated diabetic ketoacidosis, hyperalimentation, alkalosis

• Increasedexcretion:

– hyperparathyroidism, hypomagnesaemia, renal tubular defect, dialysis

• Dilution:

– volume expansion

• Chronic alcohol abuse

• Muscleweakness • Hemolysis

– depletion of 2,3-diphosphoglycerate • Respiratoryfailure

– Severe hypophosphatemia in critically ill patients

• Rhabdomyolysis: is the rapid breakdown of skeletal muscle tissue. Myoglobin released by muscle destruction may lead to acute renal failure.

Artefactual – hemolysis or delay in separation of blood samples

• Chronic renal failure

• Hypoparathyroidism

High plasma calcium and phosphate levels promote metastatic calcification which is defined as the deposition of calcium salts in previously normal tissues

malabsorption, malnutrition, alcoholism, diuretics,

chronic mineralocorticoid excess

Tetany, agitation, ataxia, tremors, convulsions

renal failure is the most important cause

High levels > 6 mg/L can cause respiratory paralysis and cardiac arrest

Two or more endocrine tumor types, occur as a part of one of the defined MEN syndromes, in a single patient and there is evidence for either a causative mutation or hereditary transmission

a mutation in the MEN1, tumor-suppressor gene

mutations in the RET proto-oncogene. MEN2 has three clinical variants referred to as MEN2A, MEN2B and MTC only.

autosomal dominant disorders

characterized by occureceof tumors predominanntly in the anterior pituitary, parathyroid and pancreatic islets

MedullaryThyroidCancer(MTC), Pheochromocytoma, Parathyroid adenoma

MedullaryThyroidCancer,Marfanoid habitus/mucosal neuroma, Pheochromocytoma

• Parathyroidtumors

• Entero-pancreatic endocrine tumors (Gastrinoma, Insulinoma, Vipoma, Glucagonoma)

• Pituitarytumor(mostlyprolactinoma).

• Other endocrine and non-endocrine neoplasms including

adrenocortical and thyroid tumors, lipomas, and carcinoids

recommending thyroidectomy to prevent or cure MTC