endo Flashcards
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decreased libido
kallman syndrome
defective hypothalmic gonadotropin realsing hormone and is associated with anosmia or hyposmia due to olfactory bulb agenesis or hypoplasia
prevents progression through puberty
postpartum women with hyperprolactinemia and prominent pituitary mass
lymphocytic hypophysiitis
empty sella
empty or partially empty sella
can hve normal pitutary function implying tht surrounding rim of pitutary tissue is functional
silent infarction csf filling
pitutary apoplexy
spontaneously postpartum ( sheehan) diabetes hypertension sicklecell anaemia shock
tt
high dose glucocorticoids if no evident visual loss
if loss of vision consiousness cn palsy them surgical decompression
?
normal or high growth hormone level
low insulin groeth levels
sequence of hormone liloss in adult gh deficiency
GH 》FSH/LH》TSH》ACTH
igf level provide useful index of therapeutic respinses but not sufficient for diagnosis
because its level can be normal in gh deficiency
contraindications of gh replacement
active neolalsm
intracranial hypertension
uncontrolled diabetes
retinopathy
?
male testosterone gnrh therapy for infertilty
females estrogen progestron
features of sellar mass
table 4031Impacted StructureClinical ImpactPituitaryHypogonadismHypothyroidismGrowth failure and adult hyposomatotropismHypoadrenalismOptic chiasmLoss of red perceptionBitemporal hemianopiaSuperior or bitemporal field defectScotomaBlindnessHypothalamusTemperature dysregulationAppetite and thirst disordersObesityDiabetes insipidusSleep disordersBehavioral dysfunctionAutonomic dysfunctionCavernous sinusOphthalmoplegia with or without ptosis or diplopiaFacial numbnessFrontal lobePersonality disorderAnosmiaBrainHeadacheHydrocephalusPsychosisDementiaLaughing seizures
stalk section phenomenon
pituitary stalk compression
disrupting pitituary of hypothalmic hormone and dopamine
decreasing all hormones except prolactin
physiologic pituary enlargement in?
adoloscent and pregnancy
prolactin suppresion by dopamine agonist doesnot neccesarily indicate tht underlying lesion is prolactinoma why?
because hyperprolactinemia caused by mass effect of nonlactotrope lesion is also corrected by treatment with dopamine agonist
mainstay of tratment with micro macro prolactinemia
oral dopamine agonist
dopamine agonist used pitutary prolactinoma
cabergoline
bromocriptine
men tend to present with larger tumors why
because features of male gonadotropin deficiency r les likely evident
causes of acromegaly
•Excess Growth Hormone Secretion
Pituitary Densely or sparsely granulated GH cell adenoma Mixed GH cell and PRL cell adenoma
Mammosomatotrope cell adenoma
Plurihormonal adenoma
GH cell carcinoma or metastases
Multiple endocrine neoplasia 1 (GH cell adenoma)
McCune-Albright syndrome
Ectopic sphenoid or parapharyngeal sinus pituitary adenoma •Extrapituitary tumor
Pancreatic islet cell tumor
Lymphoma Although these tumors usually express positive GHRH immunoreactivity, clinical features of acromegaly are evident in only a minority of patients with carcinoid disease.
Excessive GHRH
also may be elaborated by hypothalamic tumors, usually choristomas or neuromas. Presentation and Diagnosis Protean manifestations of GH and IGF-I hypersecretion are indolent and often are not clinically diagnosed for 10 years or more. Acral bony overgrowth results in frontal bossing, increased hand and foot size, mandibular enlargement with prognathism, and widened space between the lower incisor teeth. In children and adolescents, initiation of GH hypersecretion before epiphyseal long bone closure is associated with development of pituitary gigantism (Fig. 403-4). Soft tissue swelling results in increased heel pad thickness, increased shoe or glove size, ring tightening, characteristic coarse facial features, and a large fleshy nose. Other commonly encountered clinical features include hyperhidrosis, a deep and hollow-sounding voice, oily skin, arthropathy, kyphosis, carpal tunnel syndrome, proximal muscle weakness and fatigue, acanthosis nigricans, and skin tags. Generalized visceromegaly occurs, including cardiomegaly, macroglossia, and thyroid gland enlargement. The most significant clinical impact of GH excess occurs with respect to the cardiovascular system. Coronary heart disease, cardiomyopathy with arrhythmias, left ventricular hypertrophy, decreased diastolic function, and hypertension ultimately occur in most patients if untreated. Upper airway obstruction with sleep apnea occurs in more than 60% of patients and is associated with both soft tissue laryngeal airway obstruction and central sleep dysfunction. Diabetes mellitus develops in 25% of patients with acromegaly, and most patients are intolerant of a glucose load (as GH counteracts the action of insulin). Acromegaly is associated with an increased risk of colon polyps and mortality from colonic malignancy; polyps are diagnosed in up to one-third of patients. Overall mortality is increased about threefold and is due primarily to cardiovascular and cerebrovascular disorders and respiratory disease. Unless GH levels are controlled, survival is reduced by an average of 10 years compared with an age-matched control population. Laboratory Investigation Age-matched serum IGF-I levels are elevated in acromegaly. Consequently, an IGF-I level provides a useful laboratory screening measure when clinical features raise the possibility of acromegaly. Due to the pulsatility of GH secretion, measurement of a single random GH level is not useful for the diagnosis or exclusion of acromegaly and does not correlate with disease severity. The diagnosis of acromegaly is confirmed by demonstrating the failure of GH suppression to <0.4 μg/L within
Excess Growth Hormone–Releasing Hormone Secretion Central Hypothalamic hamartoma, choristoma, ganglioneuroma
Peripheral Bronchial carcinoid, pancreatic islet cell tumor, small cell lung cancer, adrenal adenoma, medullary thyroid carcinoma, pheochromocytoma
features of acromegaly
•Acral bony overgrowth results in frontal bossing, increased hand and foot size, mandibular enlargement with prognathism, and widened space between the lower incisor teeth. In children and adolescents, initiation of GH hypersecretion before epiphyseal long bone closure is associated with development of pituitary gigantism
•Soft tissue swelling results in
increased heel pad thickness,
increased shoe or glove size,
ring tightening,
characteristic coarse facial features, and a large .
generalized visceromegaly occurs, including cardiomegaly, macroglossia, and thyroid gland enlargemen
Other commonly encountered clinical features include hyperhidrosis, a deep and hollow-sounding voice, oily skin, arthropathy, kyphosis, carpal tunnel syndrome, proximal muscle weakness and fatigue, acanthosis nigricans, and skin tags. Get.
additional treatment of growth hormone secreating adenoma
surgical correction
medical treatment of growth hormone secreating adenoma
somatostatin analges octrotide lanreotide
therapeutic effects somatostatin receptors whuch r presnt of gh secreating tumors
Adverse effects are
git mainly
short-lived and mostly relate to druginduced suppression of gastrointestinal motility and secretion. Transient nausea, abdominal discomfort, fat malabsorption, diarrhea, and flatulence
. Octreotide suppresses postprandial gallbladder contractility and delays gallbladder emptying; develop long-term echogenic sludge or asymptomatic cholesterol gallstones. Other side effects include mild glucose intolerance due to transient insulin suppression, asymptomatic bradycardia, hypothyroxinemia, and local injection site discom
•gh receptor antagonst
pegvisomant
• dopamine agonist
suppress growth hormone secretion cabergoline
clinical features of cushing syndrome
Obesity or weight gain (>115% ideal body weight) Thin skin Moon facies Hypertension Purple skin striae Hirsutism Menstrual disorders (usually amenorrhea) Plethora A bnormal glucose tolerance Impotence P roximal muscle weakness Truncal obesity Acne B bruising Mental changes Osteoporosis Edema of lower extremities Hyperpigmentation Hypokalemic alkalosis Diabetes mellitus
use of petrosal sinus venous sampling
differntiate between pitutary adenoma and acth secreating tumors
treatment of choice cushing ds
selective transpenoidal resection
drugs used in cushing syndrome
somatostatin analogue
pasirotide
hyoerglycemia diabetes due to suppressed secretion of pancreatic secretion of insulin and increatins
glucocorticoids receptors antagonists
mifepristone
steroidogenic inhibitors
ketoconazole inhibit cytp450
metrapone inhibits 11b hydroxylasenelson syndrome
Adrenalectomy in the setting of residual corticotrope adenoma tissue predisposes to the development of Nelson’s syndrome, a disorder characterized by rapid pituitary tumor enlargement and increased pigmentation secondary to high ACTH levels. Prophylactic radiation therapy may be indicated to prevent the development of Nelson’s syndrome after adrenalectomy.
most common type of pituitary adenoma
non functional
MOA of AVP
Antidiuresis is mediated via binding to G proteincoupled V2 receptors on the serosal surface of the cell, activation of adenyl cyclase, and insertion into the luminal surface of water channels composed of a protein known as aquaporin 2
constriction of smmoth muscles in blood vessels and git
drug essential in sheehan syndrome
glucocorticoids
All are associated with pituitary apoplexy except-
1) Hyperthyroidism
2) Diabetes mellitus
3) Sickle cell anemia
4) Hypertension
hyperthyroidism
most common cause of GHRH mediated acromegaly
chest or abdominal carcinoid
Nelson’s syndrome is most likely seen after -
1) Hypophysectomy
2) Adrenalectomy
3) Thyroidectomy
4) Orchidectomy
adrenalectomy
Tolvaptan is approved for use in-
1) High Na
2) High K
3) High Ca
4) Low Na
low na
Treatment of lithium induced diabetes insipidus -
1) Vasopressin
2) Mineralocorticoid antagonist
3) Amiloride
4) Loop diuretic
amiloride
causes of diabetes insipidus
pituitary di
gestational DI
secondary DI due to ongibition of avp by excess fliud intake
also known as primary polydypsia
3 subcategories
dipsogenic di
psychogenic di
ioatrogenic di
nephrogenic di
most common cause of preventable mental retardation
iodine deficiency
most common cause of preventable mental retardation
iodine deficiency
cause of cretinism
congenital hypothroidism
thyroid hormone synthesis begin at 11 wks of gestation if there is no thyroid gland / hormone mother thyroid will compensate till birth so chance sof cretinism will be more in first few yrs of life
if mother is also hypothyroid during pregnancy child will be born with cretinism
TSH is realsed in pulsatile manner but single measurement is effective why
long half life of TSH
wolff chaikoff effect
excess iodine transiently inhibits thyroid iodide organification
CAUSE OF INCREASE and DECREASE IN TBG
increase in pregnancy ocp inflammatory liver ds tamoxifen serm
decrease in
androgens
nephorotic syn
seum TBG levels are increased in all type of thyrotoxcossis except
thyrotoxic factitia caused by self admininstration of thyroid hormone
function of tpo
oxidation of iodine
coupling of monoidottrosines and diiodotyrosines
antibodies found in hypothyroidism
antiTPO
antithyroglobulin
anti TSH
they r useful markers of autoimmunity
cause of myxedema in hypothyroidism
increased dermal glycosaminoglycan content traps water giving rise to skin thickening without pitting
symptoms of hypothyroidism
Symptoms Tiredness, weakness Dry skin Feeling cold Hair loss Difficulty conc entrating and poor memory Constipation Weight gain with poor appetite Dyspne a Hoarse voice Menorrhagia (later oligomenorrhea or amenorrhea) Paresthesia Impaired hearing
signs of hypothyroidism
Signs Dry coarse skin; cool peripheral extremities Puffy face, hands, and feet (myxedema) Diffuse alopecia Bradycardia Peripheral edem a Delayed tendon reflex relaxation Carpal tunnel syndrome Serous cavity effusions
effect of hypothyroidism on cvs
decrease in stroke volume
increase in periferal vascular resistence hypertension particularly diasystolic
causes of hypothyroidism
PRIMARY
Autoimmune hypothyroidism:
Hashimoto’s thyroiditis,
atrophic thyroiditis
Iatrogenic: 131I treatment, subtotal or total thyroidectomy, external irradiation of neck for lymphoma or cancer
Drugs: iodine excess (including iodine-containing contrast media and amiodarone), lithium, antithyroid drugs, p-aminosalicylic acid, interferon α and other cytokines, aminoglutethimide, tyrosine kinase inhibitors (e.g., sunitinib) Congenital hypothyroidism: absent or ectopic thyroid gland, dyshormonogenesis, TSH-R mutation
Iodine deficiency
Infiltrative disorders: amyloidosis, sarcoidosis, hemochromatosis, scleroderma, cystinosis, Riedel’s thyroiditis Overexpression of type 3 deiodinase in infantile hemangioma and other tumors
TRANSIENT
Silent thyroiditis, including postpartum thyroiditis
Subacute thyroiditis
Withdrawal of supraphysiologic thyroxine treatment in individuals with an Secondary intact thyroid
After 131I treatment or subtotal thyroidectomy for Graves’ disease
SECONDARY
Hypopituitarism: tumors, pituitary surgery or irradiation, infiltrative disorders, Sheehan’s syndrome, trauma, genetic forms of combined pituitary hormone deficiencies
Isolated TSH deficiency or inactivity
Bexarotene treatment
Hypothalamic disease: tumors, trauma, infiltrative disorders, idiopathic
myxedema coma the
long standing hypothyroidism
pt with no medication
bradycardia, hypotension , stupor , coma delayed deep tendon reflex, seizures,other features of hypothyroidism
precipitating factors
severe illness , exposure to cold , eldrly
factors tht impair respiration drugs pneumonia CHF,MI,GI bleed ,CVA
TREATMENT of myxedema coma
iv bolos levothyroxine
levothyronine t4 to t3 conversion is impaired
hydrocortisone due to impaired adrenal reserve
treat precipitating factors
why t3 is not used in long term thyroid replacement
due to short half life 3-4 daiky doses hve to be given
causes of thyrotoxcossis
CAuSES of THyRoToxiCoSiS
Primary Hyperthyroidism
Graves’ disease
Toxic multinodular goiter
Toxic adenoma
Functioning thyroid carcinoma metastases Activating mutation of the TSH receptor Activating mutation of GSα (McCune-Albright syndrome) Struma ovarii Drugs: iodine excess (Jod-Basedow phenomenon) Thyrotoxicosis Without Hyperthyroidism Subacute thyroiditis Silent thyroiditis Other causes of thyroid destruction: amiodarone, radiation, infarction of adenoma Ingestion of excess thyroid hormone (thyrotoxicosis factitia) or thyroid tissue
Secondary Hyperthyroidism
TSH-secreting pituitary adenoma
Thyroid hormone resistance syndrome: occasional patients may have features of thyrotoxicosis
Chorionic gonadotropin-secreting tumorsa
Gestational thyrotoxicosisa aCirculating TSH levels are low in these forms of secondary hyperthyroidism.
difference bw thyotoxicosis and hyperthyroidism
?
antibodies in graves ds
TSI
can TSI cross placenta
yes so can cause thyrotoxcossis in fetus
antithyroid drugs given to mother will protect the fetus also as they will also cross placenta
triad of graves ds
graves opthalmopathy
eye signs
grittiness tearing proptosis
corneal damage
periorbital edema
scleral injection
chemosis
optic nerve compression
dermopathy
most frequently over ant and lateral aspect over lower leg
pretibial myxedema
non inflamed indurated plaque
acropathy
form of clubbingantithyroid druds
propylthiouracil
carbimazole
All inhibit the function of TPO, reducing oxidation and organification of iodide. These drugs also reduce thyroid antibody levels by mechanisms that remain unclear, and they appear to enhance rates of remission. Propylthiouracil inhibits deiodination of T4 →
which antithyroid prevents t4>t3 conversion
propylthiouracil
why propylthiouracil should not be given to children and pregnancy
hepatotoxic
prevention of radioiodine induced throtoxic crisis
preadministtration of amtithyroid drugs decrease the hormone level but these drugs should be discontinued before radionucleotide treatment because it will prevent its uptake
treatment of thyrotoxic crisis or thyroid strom
signs and symptoms
fever delirium seizures , vomiting diarrohea jaundice
hyperthermia arrythymia cardiac failure
precipiting factors acute illness (e.g., stroke, infection, trauma, diabetic ketoacidosis), surgery (especially on the thyroid), or radioiodine treatment of a patient with partially treated or untreated hyperthyroidism
drugs
propylthiouracil doc will inhibit t4>t3 conversion
methimazole
iodine blocks thyroid hormone synthesis by wolf chaikoff effect
propanolol esmolol
adrenergic manifestations also prevent t4>t3conversion
signs and symptoms of thyrotoxcossis
nS AnD SymPTomS of THyRoToxiCoSiS (DESCEnDing oRDER of fREquEnCy) SYMPTOMS Hyperactivity, irritability, dysphoria Heat intolerance and sweating alopecia Palpitations Fatigue and weakness Weight loss with increased appetite Diarrhea Polyuria Oligomenorrhea, loss of libido SIGNS Tachycardia; atrial fibrillation in the elderly Tremor Goiter Warm, moist skin Muscle weakness, proximal myopathy Lid retraction or lag Gynecomastia
effect of thyrotoxcossis on cvs
sinus tachycardia palpitations increased stoke volume high output cardiac failure widened pulse pressure atrial fibrillation
causes of throiditits
Acute Bacterial infection: especially Staphylococcus, Streptococcus, and Enterobacter Fungal infection: Aspergillus, Candida, Coccidioides, Histoplasma, and Pneumocystis Radiation thyroiditis after 131I treatment Amiodarone (may also be subacute or chronic) Subacute Viral (or granulomatous) thyroiditis Silent thyroiditis (including postpartum thyroiditis) Mycobacterial infection Drug induced (interferon, amiodarone) Chronic Autoimmunity: focal thyroiditis, Hashimoto’s thyroiditis, atrophic thyroiditis Riedel’s thyroiditis Parasitic thyroiditis: echinococcosis, strongyloidiasis, cysticercosis Traumatic: after palpation
jod basedow effect and wolf chaikoff effect
jod basedow thyroid hormone synthesis is increased due to increased iodine
factors altering thyroid function in pregnacy
Five factors alter thyroid function in pregnancy:
(1) the transient increase in hCG during the first trimester, which stimulates the TSHR;
(2) the estrogen-induced rise in TBG during the first trimester, which is sustained during pregnancy
; (3) alterations in the immune system, leading to the onset, exacerbation, or amelioration of an underlying autoimmune thyroid disease (see above);
(4) increased thyroid hormone metabolism by the placenta; and
(5) increased urinary iodide excretion, which can cause impaired thyroid hormone production in areas of marginal iodine sufficiency
effect of amidorone on thyroid gland
both hypo/hyper
initally hypo due to wolff chaikoff effect
inhibits deiondinase and thyroid hormone receptors
inc t3 dect4 inc tsh
sometiime jod basedow effect occurs thyroid hormone synthesis becomes excessive as a result of inc iodine amt dure to underlying thyroid abnormality like graves or mng
subacute throiditits also known as
This is also termed
de Quervain’s thyroiditis,
granulomatous thyroiditis,
viral thyroiditis
cause virus
3 phasss
1) thyrotoxic phase,
, T4 and T3 levels are increased, reflecting their discharge from the damaged thyroid cells, and TSH is suppressed
(2) hypothyroid phase, and-10). During this destructive phase, radioactive iodine uptake is low or undetectable. After several weeks, the thyroid is depleted of stored thyroid hormone and a phase of hypothyroidism typically occurs, with low unbound T4 (and sometimes T3) and moderately increased TSH levels
(3) recovery phase.
features of subacute
history of upper respiratory tract infection
sore throat
tender goiter
tt of subacute
aspirin glucocorticoids beta blockers levothyroxine no role of antithyroid drugs
painless thyroidits
silent thyrodiits
post partum thyroidits diffrernce from subacute are
painless
normal esr
pressence of tpo
reidel thyrodiits
insidous onset
painless
dense fibrosis extend outside thyroid caosule
local compression symptoms esophageal and neck veins
hard nom tender
asymmetric fixed
difficulty to differenciate feom malignancy
ses
due to severe diseases
due to realses of cytokines
most common hormone pattern
low t3 total and unbound
normal t4
normal tsh
cause due to impair peripheral conversion of t4>t3 leading to inc reversed t3 amd normal t4 and tsh
decreasing catabolism in sarved or ill
very sick pts dec in total t4 and t3
types of goiter
diffuse nontoxic
difuse enlargement absent of nodules
non toxic multonodiukar goiter
toxic multonodiula goitet
environmental goitrogens
Endemic goiter is also caused by exposure to environmental goitrogens such as cassava root, which contains a thiocyanate; vegetables of the Cruciferae family (known as cruciferous vegetables) (e.g., Brussels sprouts, cabbage, and cauliflower); and milk from regions where goitrogens are present in grass.
histologic changes
cytic areas with blood
lymphocytic invasuon ?
risk facotrs of thyroid ca
k fACToRS foR THyRoiD CARCinomA in PATiEnTS wiTH THyRoiD noDulE
History of head and neck irradiation, including total-body irradiation for bone marrow transplant and brain radiation for childhood leukemiaExposure to ionizing radiation from fallout in childhood or adolescenceAge <20 or >65 yearsIncreased nodule size (>4 cm)New or enlarging neck massMale genderFamily history of thyroid cancer, MEN 2, or other genetic syndromes associ-ated with thyroid malignancy (e.g., Cowden’s syndrome, familial polypo-sis, Carney complex)Vocal cord paralysis, hoarse voiceNodule fixed to adjacent structuresExtrathyroidal extensionLateral cervical lymphaden
control of
hpa control gluco and adrenal androgen
raas mineralocorticoid
low dose dexamethasone suppreses
normal person
high dose dexamethasone suppresses
pitutary
acth secreting tumor not ectopic
glucocorticoids act at
nuclear glucocorticoids receptors
cause of antiimfammotory action of glucocorticoids
transrepression of proinflammatory genes
cortisol is inactivated to corticosterone by
enzyme found predominantly in kidney
signifiacance Cortisol and aldosterone bind the mineralocorticoid receptor (MR) with equal affinity; however, cortisol circulates in the bloodstream at about a thousandfold higher concentration. Thus, only rapid inactivation of cortisol to cortisone by 11β-HSD2 prevents MR activation by excess cortisol, thereby acting as a tissue-specific modulator of the MR pathway. In addition to cortisol and aldosterone, deoxycorticosterone (DOC) (F
cushing ds
pitutary corticotrope adenoma
most common cause of cushing syn
exogenous corticosteroids
causes of cushing
Causes of Cushing’s Syndrome
ACTH-Dependent Cushing’s
Cushing’s disease (= ACTH-producing pituitary adenoma) Ectopic ACTH syndrome (due to ACTH secretion by bronchial or pancreatic carcinoid tumors, small-cell lung cancer, medullary thyroid carcinoma, pheochromocytoma and others)
ACTH-Independent Cushing’s
Adrenocortical adenoma
Adrenocortical carcinoma
signs and symptoms of cushing ds
SignS AnD SymPTomS of CuSHing’S SynDRomE
Body Compartment/ System
•Body fat
Weight gain, central obesity, rounded face, fat pad on back of neck (“buffalo hump”)
•Skin
Facial plethora, thin and brittle skin, easy bruising, broad and purple stretch marks, acne, hirsutism
•Bone
Osteopenia, osteoporosis (vertebral fractures), decreased linear growth in children
•Muscle
Weakness, proximal myopathy (prominent atrophy of gluteal and upper leg muscles with difficulty climbing stairs or getting up from a chair
•Cardiovascular system Hypertension, hypokalemia, edema, atherosclerosis
•Metabolism ) Glucose intolerance/diabetes, dyslipidemia •Reproductive system Decreased libido, in women amenorrhea (due to cortisol-mediated inhibition of gonadotropin release)
•Central nervous system Irritability, emotional lability, depression, sometimes cognitive defects; in severe cases, paranoid psychosis
• Blood and immune system increased susceptibility to infections, increased white blood cell count, eosinopenia, hypercoagulation with increased risk of deep vein thrombosis and pulmonary embolism
effect of glucocorticoids on carbo fats and proteins
gluconeogenesis
lipolysis
proteolysis catabolism
why excess cortisol causes hypertension
because will not inactivated by kidney
more minerlacorticoid effect
hyperpigmentation seen in which cusing ds
ectopic acth
occurs over knuckles scar mark skin area exposed to friction
effect of ocp on cortisol level
increase cortisol binding protein so inc in total cortisone
can give false positive result in cushing syndrome screening
failure of dexamethasone suppression but 24 hr urinary free cortisol tells only abt free so no effect on this test
how does concurrent intake of antiepileptics and rifampicin
effect screening
inactivate dexamethasone
conns syndrome
aldosterone producing adrenal adenoma
causes of mineralocoricoid excess
SES of minERAloCoRTiCoiD ExCESS
Causes of Mineralocorticoid Excess
Primary Aldosteronism
Adrenal (Conn’s) adenoma
Autonomous aldosterone excess .
Bilateral (micronodular) adrenal hyperplasia
Autonomous aldosterone excess
Glucocorticoid-remediable hyperaldosteronism (dexamethasone-suppressible hyperaldosteronism)Crossover between the CYP11B1 and CYP11B2 genes results in ACTH-driven aldosterone production
Other Causes
Syndrome of apparent mineralocorticoid excess (SAME)Mutations in HSD11B2 result in lack of renal inactivation of cortisol to cortisone, leading to excess activation of the MR by cortisol
Cushing’s syndrome Cortisol excess overcomes the capacity of HSD11B2 to inactivate cortisol to cortisone, con-sequently flooding the MR
Glucocorticoid resistance Upregulation of cortisol production due to GR mutations results in flooding of the MR by cortisol
Adrenocortical carcinoma
Autonomous aldosterone and/or DOC excess
Congenital adrenal hyperplasia
Accumulation of DOC due to mutations in CYP11B1 or CYP17A1
Progesterone-induced hypertensionProgesterone acts as an abnormal ligand due to mutations in the MR gene
Liddle’s syndrome
Mutant ENaC β or γ subunits resulting in reduced degradation of ENaC keeping the mem-brane channel in open conformation f
liddles syn
Liddle’s syndrome
Mutant ENaC β or γ subunits resulting in reduced degradation of ENaC keeping the mem-brane channel in open conformation for longer enhacing mineralocorticoid excess
clinaical manifestations of excess mineralocorticoid
hypokalemic hypertension hallmark na level normal potassium depletion metabolic alkalosis muscle weakness myopathy due to hypokalemia and alkalosis. periferal edema
adrenal insufficiency
primary cause is adrenal
secondary pitutary or hypothalmus
if adrenal all 3 mineralo, gluco, androgen
if secondary acth effected so no effect on mineralocorticoid because it is controlled by raas effect on glucocorticoids and androgens
difference between primary and secondary adrenal insufficiency
PRIMARY
Hyperpigmentation due to excess of proopiomelanicortin
SECONDARY
albaster colored pale skin due diffeciency of proopiomineralocortin
cause of hyponatremia in primary and secondary adrenal insufficiency
primary dec mineralocorticoid
sec due to cortisol deficiency inc adh leading to siadh
signs and symptoms of adrenal insufficiency
•Signs and Symptoms Caused by Glucocorticoid Deficiency
TB>Fatigue,
lack of energy
Weight loss,
anorexia
Myalgia,
joint pain
Fever
Normochromic anemia, lymphocytosis, eosinophilia
Slightly increased TSH (due to loss of feedback inhibition of TSH release)
Hypoglycemia (more frequent in children)
Low blood pressure, postural hypotension
Hyponatremia (due to loss of feedback inhibition of AVP release)
•Signs and Symptoms Caused by Mineralocorticoid Deficiency (Primary Adrenal Insufficiency Only) Abdominal pain, nausea, vomiting Dizziness, postural hypotension Salt craving Low blood pressure, postural hypotension Increased serum creatinine (due to volume depletion )Hyponatremia Hyperkalemia
•Signs and Symptoms Caused by Adrenal Androgen Deficiency
Lack of energy
Dry and itchy skin (in women)
Loss of libido (in women)
Loss of axillary and pubic hair (in women)
•Other Signs and Symptoms
Hyperpigmentation (primary adrenal insufficiency only) (due to excess of proopiomelanocortin [POMC]-derived peptides)
Alabaster-colored pale skin (secondary adrenal insufficiency only) (due to deficiency of POMC-derived peptides)
rule of 10
10% bilateral
10%exrtraadrenal
10% malignant
difference between pheochromocttoma and paraganglioma
who restrict pheochromocttoma to adrenal tumor
and paraganglioma for tumors if al other sites
clinical features of pheochromocytoma
CliniCAl fEATuRES ASSoCiATED wiTH PHEoCHRomoCyTomA, liSTED by fR£EquEnCy of oCCuRREnCE
- Headaches
- Profuse sweating
- Palpitations and tachycardia
- Hypertension, sustained or paroxysmal 5. Anxiety and panic attacks 6. Pallor 7. Nausea 8. Abdominal pain 9. Weakness 10. Weight loss 11. Paradoxical response to antihypertensive drugs 12. Polyuria and polydipsia 13. Constipation 14. Orthostatic hypotension 15. Dilated cardiomyopathy 16. Erythrocytosis 17. Elevated blood sugar 18. Hypercalcemia
classic triad of pheochromocytoma
palpitations
headache
profuse sweating
biochemical and imaging test for diagnosis of pheochromocytoma
CHEmiCAl AnD imAging mETHoDS uSED foR DiAgnoSiS of PHEoCHRomoCyTomA AnD PARAgAngliomA Diagnostic Method 24-h urinary tests Catecholamines Fractionated metanephrines Total metanephrines Plasma tests Catecholamines Free metanephrines Imaging CT M MRI MIBG scintigraphy Somatostatin receptor scintigraphya Fluoro-DOPA PET/CT
false positive and false negative result of pheochromocytoma
exclude dietary or drug-related factors (withdrawal of levodopa or use of sympathomimetics, diuretics, tricyclic antidepressants, alpha and beta blockers) that might cause false-positive results and then to repeat testing or perform a clonidine suppression test (i.e.,
causes of karyotypic abnormalities in turner and klinefelter
turner
paternal nondysjunction
structural abnormality
mosaicism.
klinefelter
nondysjunction
mosaicism
features of klinefelter
•late puberty
•gynaecomastia
tall long legs
facial body and pubic hair diminshed
small penis
testicular atrophy
lower IQ
• cardiovascular
mitral valve prolapse
• type 2 diabetes
metabolic syndrome
autoimmune ds
breast cancer
osteoporosispathophysiology of klinefelter
•loss of sertoli leads to increase in fsh (as inhibin is decreased which inhibits fsh)
increase the synthesis of aromatase in leydig cells leading to increse in conversion of androgen to estradiol
•x chromosome with shorter cag repeats is inactivated leaving x chromosome with longer cag repeats on whic testosterone cannot act which along with inc conersion to estrogen causes feminization
clinical manifestations of turner
short stature cubitus valgus knuckles knuckles dimple knuckle sign short 4th metatarsal or 4th metacarpal. shield chest widely spaced nipples pubic hair normal webbed neck in adult lymphedema of hands limbs neck in infancy cvs - left sided.heart ds streak gonads primary amenorrhea horse shoe kidney
