Learning Objectives: Will be able to select appropriate
diagnostic lab testing when presented with a case study
representing the most common disorders of the pituitary, thyroid,
adrenal and parathyroid glands, and arrive at a diagnosis based on
properly interpreting the results. Will be able to select and
interpret lab test results that are used to manage/monitor the most
common disorders of the pituitary, thyroid, adrenal and parathyroid
glands. Will be able to recognize and diagnose common autoimmune
and paraneoplastic syndromes (ectopic hormones) that present as
primary endocrine disorders
Slide 4
and the lab tests we use for diagnosis and monitoring Negative
Feedback Control To Understand Endocrine Physiology and Pathology,
and the lab tests we use for diagnosis and monitoring we have to
understand Negative Feedback Control
Slide 5
Negative Feedback Control Grandma Grandson
Slide 6
90 degrees !!
Slide 7
Negative Feedback Control Grandma Grandson Tertiary Secondary
Primary
Slide 8
Negative Feedback Control Grandma Grandson
Slide 9
Negative Feedback Control Grandma Grandson Tertiary Secondary
Primary Ectopic
Negative Feedback Control Hypothalamus Pituitary Target organs
Peripheral gland Releasing hormones Stimulating hormones hormones
Over Production
Slide 12
Negative Feedback Control Hypothalamus Pituitary Target organs
Peripheral gland Releasing hormones Stimulating hormones hormones
Under Production
Slide 13
The Hypothalamic-Pituitary Axis Hypothalamus: CEO Consolidates
signals from cortex, autonomics, environment, feedback. Produces:
TRH, GHRH, CRH, GRH, (stimulatory), Vasopressin and oxytocin
Produces: dopamine to inhibit pituitary Prolactin Pituitary: Vice
President Receives precise signals from the hypothalamus Releases
hormones that influence primary endocrine glands Intermediate
Slide 14
Endocrine glands: The Pituitary Secretes: Anterior Lobe:
(produces/secretes) ACTH Adrenals hGH Liver, other TSH Thyroid
gland FSH Gonads LH Gonads PRL(LTH) mammary ; gonads Intermediate
Lobe: (produc/secret) MSH melanocytes Posterior Lobe: (secretes
only) ADH kidney, arteries Oxytocin uterus, brain (will not be
discussing post. Pituitary) /Ovaries
Slide 15
Hypothalamic Diseases: No diseases of overproduction of
releasing hormones, Ectopic CRF: pulmonary carcinoid tumors
Cushings Syndrome Underproduction, leading to hypopituitarism,
occurs with: Mass lesions: craniopharyngiomas, metastases Radiation
damage: occurs when brain receives RT Infiltrative lesions: ie.
Sarcoidosis, histiocytosis Infections: i.e. tuberculous
meningitis-> hypothalamus Traumatic brain injury Take Home
Point: Hypopituitarism -> R/O Hypothalamic Dis.
Slide 16
Pituitary Adenomas: 800,000/yr US Prevalence in population:
16.7%* ; May be part of MEN1 Overproduction of stim./trophic
hormones: Somatotroph Adenoma: 27 % of pit. Adenomas Produces GH
which is pulsatile; dont assay. IGF-1. (GH stimulates IGF-1) stable
levels. Assay. Acromegaly: excess growth bones, soft tissues
Corticotroph Adenoma: 8% of pit. Adenomas Produces ACTH, which in
turn stimulates corticosteroids. This is Cushings Disease which
will be discussed again under Adrenal Diseases. * Ezzat et. al.,
Cancer. 2004, Aug 1; 101(3) 613-9
Slide 17
Pituitary Adenomas: (continued) Prolactinoma: - 18% Pituitary
Adenomas Galactorrhea, libido, HA, amenorrhea ( LH, FSH ) Elevated
Prolactin levels: Secreted by prolactinoma Or: non-functioning
macroadenoma obstructing hypothalamic inhibition. MRI: to confirm
cause Treatment/monitoring: If small: Dopamine analog
bromocriptine, cabergoline. If large, transphenoidal adenomectomy
Monitor prolactin levels
Slide 18
Pituitary Adenomas (continued): FSH/LH Adenomas: 5 % of pit.
Adenomas Produces FSH (4.4%) or LH Produce gonadal hyperstimulation
Produces high Estradiol, testosterone Thyrotroph Adenoma: 1.2 % of
pit. Adenomas Produces TSH, which in turn stimulates Thyroid
hormones. This is Secondary Hyperthyroid which will be discussed
again under Thyroid Diseases. Non-functioning Adenomas: 32% (most
gonadotroph) Others: 9 % Percentage data: Pathology of the Human
Pituitary Adenomas, www.ncbi.nlm.nih.gov
Slide 19
Hypopituitarism Global: Sheehans pituitary infarction after
post-partum hemorrhage Pituitary Apoplexy sudden hemorrhage into
pituitary Bleed often occurs into a pituitary adenoma Sudden onset
of severe headache, diplopia, hypopituitarism Sudden onset of ACTH
defic cortisol hypotension, glucose Other: radiation, infiltrative
(hemochromatosis), granuloma, TBI, tumor/metastasis, infectious,
autoimmune Symptoms: pan-hypopit: Hypocortisolism, hypothyroid
Labs: prolactin, TSH, FT4, IGF-1, ACTH, FSH, LH, cortisol and
cosyntropin stimulation test (see Adrenal Insufficiency)
Slide 20
Hypopituitarism Selective: Sxs are same as hypo function of
target organ Causes: genetic/congenital, tumors, radiation, TBI,
autoimmune, infarct Lab tests: Growth Hormone Deficiency: GH
stimulation test; IGF-1 Adrenal Corticotrophic Hormone Deficiency:
early AM cortisol, Cosyntropin stimulation test, ACTH (see adrenal
insufficiency) Thyroid Stimulating Hormone Deficiency: TSH, FT4,
FT3 LH/FSH Deficiency: Rule out Prolactinoma ! Women:
Pre-menopause: Estradiol, LH, FSH, abnormal periods Post-menopause:
LH, FSH Men: LH, FSH and testosterone
The Adrenal Glands ( Most complicated, so will cover first
)
Slide 23
The Adrenal Cortex: 3 Parts Mineralocorticoids (aldosterone)
Aldosterone Regulated: Angiotensin II Glucocorticoids Cortisol
Regulated: ACTH Androgens ACTH, other Adrenal Medulla Epinephrine,
Nor-Epi Fight or flight
Hypercortisolism: Cushings Syndrome Definition: Chronic high
levels of cortisol in the blood, either endogenous or exogenous
Causes: (women > men 3:1 ; age 20-50) Exogenous glucocorticoids
(steroids) ACTH secreting pituitary adenoma (Cushings Disease)
Adrenal adenoma or hyperplasia Adrenal carcinoma Ectopic ACTH:
Small Cell Ca lung, medullary Ca thyroid Ectopic CRF: Pulmonary
Carcinoid tumors
Symptoms of Cushings Syndrome: Truncal/abdominal Obesity thin
limbs buffalo hump hypertension glucose intolerance moon face easy
bruising striae proximal muscle weakness bone loss osteonecrosis of
femur head menstrual irregularities Hirsutism (because ACTH stim.
Androids) Emotional instability/depression
Slide 32
Hypercortisolism (Cushings Syndrome) Diagnostic Lab Tests: A
single test cannot be used to diagnose hypercortisolism: Increase
in daily urinary cortisol excretion (gold standard) High midnight
salivary cortisol levels Increase in late evening serum cortisol
levels Low dose Dexamethasone challenge A single test cannot be
used to differentiate the cause of HC Primary hypercortisolism:
adenoma of adrenal cortex: high serum cortisol, low plasma ACTH
because of neg. feed back Secondary hypercortisolism: adenoma of
pituitary: high serum cortisol, high plasma ACTH,
Non-ACTH-dependent. Ectopic ACTH production : high serum cortisol,
high plasma ACTH
Slide 33
Simplified Algorithm for Hypercortisolism R/O exogenous
steroid, then confirm hypercortisol: low dose Dex. suppression 24
hr urine, midnight salivary cortisol High Dose Dexameth. S
uppression Pituitary Adenoma or ectopic CRF (High ACTH) MRI: no
mass -> ectopic CRF (High CRF) MRI: tumor in Pituitary->
Cushings Dis. Adrenal or Ectopic: Measure ACTH low ACTH: Adrenal
source high ACTH Ectopic ACTH YesNo
Slide 34
Hypercortisolism (Cushings) Diagnostic Lab Tests: (continued)
CRH stimulation test Usually done with equivocal plasma ACTH levels
Indicated to differentiate Cushings disease from Cushings syndrome
and ectopic ACTH Pituitary tumor will show increase in ACTH and
cortisol levels Adrenal tumor and ectopic ACTH production will not
show any increase
Slide 35
Cushings Syndrome Treatment:
Slide 36
Diseases affecting the Adrenal Gland Adrenal Insufficiency
Slide 37
1 o Adrenal Insufficiency : Addisons Disease Addisons Disease:
a disorder characterized by inadequate secretion (usually
progressive) of hormones by the adrenal cortex. AKA: chronic
adrenal insufficiency, hypocortisolism, hypoadrenalism Causes:
Autoimmune: 75-85 % of all cases of Primary Adrenal Insufficiency
Autoimmune polyendocrine syndrome type 1 & 2 (60%, female)
Isolated autoimmune adrenal insufficiency (40%, > up to 30 yo)
Immune-mediated destruction of the adrenal cortex Humoral (Abs)
& Cellular (cytoxic T lymphs/activated macrophages) Abs to all
3 zones of the Adrenal Cortex are present in 60-75% Studies show
that by the time AM Cortisol is low, disease is advanced Other: TB,
hemorrhage, surgical, infarction, neoplastic, amyloid
Slide 38
1 o Adrenal Insufficiency : Symptoms anorexia
Slide 39
Addisons Disease: Negative Feedback Control Hypothalamus
Pituitary Target organs Adrenal glands CRH ACTH adrenal hormones
Under Production
Slide 40
Why hyperpigmentation occurs in Addisons: Proopiomelanocortin
(POMC) ACTH MSH
Slide 41
Differential Dx of Adrenal Insufficiency Cosyntropin
Stimulation Test (ACTH analog to determine ACTH dependency ) Does
cortisol increase? ACTH Low-> Exog. Steroids w/suppressed H-P-A
glands Low CRF, ACTH ACTH high -> Addisons (1 o AI ) CT/MRI
adrenals Supplement hydrocortisone fludrocortisol 2 o or 3 o
Adrenal Insuff. (Basal ACTH low; CRH?) CT/MRI Assay CRF: CRH high:
2 CRH low: 3 Supplement hydrocortisone, (No aldosterone ) NoYes
ACTH? Also: CRH Stim. Test: pos-> 3 o ; no resp. -> 2 o AM
serum or salivary cortisol; 24 hr urinary.
Slide 42
The Thyroid Gland Secretes T4 and T3 Target organs: most/all
cells of body Promotes metabolism Basal metabolic rate Oxygen
consumption growth & development
Slide 43
Thyroid Hormones: Negative Feedback Control Hypothalamus
Pituitary Target organs Thryroid glands TRH TSH T4 and T3 hormones
Ectopic: Paraneoplastic Autoimmune
Slide 44
Diseases of the Thyroid Gland Hyperthyroidism
Slide 45
Symptoms of of Hyperthyroid Hyperthyroid
Slide 46
Hyperthyroidism: Primary Thyroid Hormones T4 T3 Target organs
Hypothalamus TRH Anterior Pituitary TSH
Slide 47
Hyperthyroidism: Secondary Thyroid Gland T3 T4 Hypothalamus TRH
Anterior Pituitary TSH Target Organs
Slide 48
Hyperthyroidism Causes: Graves Disease: (ectopic TSH)
Autoimmune: antibody is TSH Receptor Ab (TSHR-Ab) which has
affinity for the TSH receptor and stimulates T4 and T3 hormone
production. TSHR Ab can be measured. Gland is diffusely enlarged
secondary to overstimulation High radioiodine uptake; low TSH and
TRH Toxic adenoma/toxic multinodular goiter: (1 o Hyperthyroid )
Focal and/or diffuse hyperplasia of TSH-independent cells. High
radioiodine uptake; low TSH and TRH
Slide 49
Hyperthyroidism Causes (cont) : Thyroiditis: (inflammation of
the thyroid gland) Produces transient hyperthroidism, due to
release of preformed hormone, (thyroglobulin), then hypothyroid.
Gland is diffusely enlarged and tender 2 o to inflammation No to
low radioiodine uptake; initially suppressed TSH
Exogenous/factitious: Patient takes thyroxine for Wt loss/buzz No
to low radioiodine uptake; suppressed TSH. Functional thyroid Ca
with mets: High TSH, high RI Uptake 2 o due to pituitary adenoma:
high TSH; high RI uptake
Slide 50
Hyperthyroid Lab Work-up: Check TSH, FT4, FT3 High FT3 &
FT4 and low TSH Primary Hyperthyroidism: adenoma or multi- nod.
goiter Euthyroid Sick Syndrome High FT3 & FT4 and high TSH 2 o
Hyperthyroid: TSH producing Pit. Adenoma Radioactive thyroid Uptake
sometimes used
Slide 51
Hyperthyroid Treatment: Pharmacologic: Beta blockers (favors
formation RT3), anxiolytics, Suppressive: PTU (use in Pregnancy);
methimazole Radioiodine ablation: will then need replacement
therapy Thyroidectomy: will then need replacement therapy When
monitoring suppressive or replacement therapy: check TSH, FT$
plus/minus FT3
Slide 52
Diseases of the Thyroid Gland Hypothyroidism
Slide 53
Slide 54
Hypothyroidism: Primary Thyroid Hormones T4 T3 Target organs
Hypothalamus TRH Anterior Pituitary TSH
Slide 55
Hypothyroidism Causes of 1 o : 99% of cases of Hypothyroidism
are primary The etiology should always be determined because: Some
cases are transient e.g. post-partum; sub-acute thyroiditis (viral)
May be caused by a drug e.g. amiodarone, lithium It may be the
first manifestation of hypothalamic or pituitary disease Hashimotos
Thyroiditis: Chronic autoimmune 1 o Hypothyroidism Autoimmune:
Anti-thyroglobulin Ab; Anti-thyroid peroxidase Ab. Prevalence: 47
per 1000 Gender: 5-8 times more commen in women S/P thyroidectomy,
radioiodine therapy, radiation therapy Drugs: lithium,
amiodarone
Slide 56
Hypothyroidism: Other causes of 1 o : Iodine deficiency or
excess Overtreatment with methimazole or PTU Infiltrative disease:
fibrous thyroiditis (Reidels ), sarcoid, hemochromatosis,
scleroderma, amyloidosis Infection: TB, Pneumocystis Transient
Post-partum thyroiditis
Slide 57
Hypothyroidism: 2 o and 3 o Thyroid Hormones T4 T3 Target
organs Hypothalamus TRH Anterior Pituitary TSH
Slide 58
Hypothyroidism, Secondary & Tertiary: Also called Central
Hypothyroidism: less than 1 % Caused by any of the causes of
Hypopituitarism previously reviewed Inactivating mutations in the
gene for TRH, TSH, or the gene for TRH or TSH receptor Caused by
any damage to the hypothalamus as previously reviewed
Slide 59
Hypothyroid Lab Work-up: Check TSH, FT4, FT3 Low FT3 & FT4
and low TSH: Central Hypothyroid ? Secondary Hypothyroidism: look
for other Pit. deficiency ? Tertiary Hypothyroidism: look for other
Hypothal. Defics Low FT3 & FT4 and high TSH: 1 o Hypothyroid:
replace with synthroid, monitor TSH If recently ill, ? sick
euthyroid and repeat all TFTs in 2-3 wks
Slide 60
aare The Parathyroid Glands Are generally 4 in number Sit
behind the lateral lobes of the thyroid. parathyroid hormone (PTH)
Produce parathyroid hormone (PTH) Calcium phosphorus Regulate
Calcium and phosphorus in body and bones
Slide 61
Actions of Parathyroid Hormone: Increases PO4 excretion
Primary Hyperparathyroidism Diseases Causing Hypercalcemia,
PTH-mediated: Primary Hyperparathyroidism Most commonly caused by
solitary parathyroid adenoma Results in increased PTH, increased Ca
and decreased phosphorus hypercalcemia Primary Hyperparathyroidism
and Malignancy (paraneoplastic) account for > 90 % of cases of
hypercalcemia Cured by surgical excision of adenoma
Slide 64
Diseases causing hypercalcemia, - PTH Mediated (contd):
Familial Hypocalciuric Hypercalcemia Calcium-sensing receptor
mutation on Parathyroid Gland Causes increased PTH secretion
Decreased urinary excretion of Ca ++ Increased serum Calcium
Slide 65
Diseases of the Parathyroid Gland: Secondary
Hyperparathyroidism caused by Renal Disease: Ca due to increased
PO4 and decreased Vitamin D production PO4 and Vitamin D causes Ca
Decreased Ca causes increased PTH Increased PTH causes Bone &
joint pain Negative feedback causes gland hypertrophy and increased
PTH production
Slide 66
Diseases of the Parathyroid Gland: Tertiary Hyperparathyroidism
of Long-standing Renal Disease: Ca due to PO4 and Vitamin D
production Ca causes increased production of PTH eventually Ca PTH
of long duration eventually Ca Negative feedback causes gland
hypertrophy and increased PTH production PO4 and Vitamin D causes
Ca
Diseases causing hypercalcemia, Non-PTH Mediated: Malignancy
(paraneoplastic/ectopic) Tumor cells produce PTHrP PTHrP has
similar structure as PTH Breast Ca, squamous cell lung Ca, head
& neck Ca, kidney/bladder Ca Vitamin D Intoxication
Granulomatous Disease Thiazide diuretics Lithium
Diseases of the Parathyroid Gland Hypoparathyroidism
Slide 74
Hypoparathyroidism/Low Ca causes: S/P thyroidectomy or other
neck surgery S/P radioiodine therapy for Graves Autoimmune
hypoparathyroidism Infiltration of parathyroids Hypomagnesemia
Vitamin D deficiency dietary Vitamin D3 deficiency advanced chronic
kidney disease Vitamin D3 (Calcitriol) resistance Inactivation of
Vit. D through cytochrome P-450 by various drug combinations (e.g.
anti-epileptics)
Slide 75
Lab Tests for Hypocalcemia and their interpretation:
PTHPO4Mg++Vit D2Vit. D3Creat. Hypoparathyroid -- -- / --
Hypomagnesemia - / -- PTH Resistance -- -- / -- Vitamin D Defic.- /
-- variable -- CKD - / --
Slide 76
Endocrine glands: In Summary We discussed diagnostic lab tests
that are used to diagnose the most common disorders of the
pituitary, thyroid, adrenal and parathyroid glands. We also
discussed the lab tests that are used to manage/monitor the most
common chronic conditions of these same endocrine glands. Finally,
we discussed how to recognize and diagnose common autoimmune and
paraneoplastic syndromes that present as primary endocrine
disorders, by using lab test algorithms. /Ovaries
Slide 77
to unwrap the mysteries I am hopeful that I have provided you
with some helpful tools to unwrap the mysteries of endocrine
disorders. And, hopefully you have replaced this with this when you
think about endocrine disorders !! Thank you for your attention.
Questions ??
