Endocrinology

NPLEx Review
Kimberly Sanders, ND
 Type 1 DM
• Autoimmune pancreatic beta cell destruction leading to insulin
deficiency and elevated glucose
• Sxs: fatigue, vision changes, bed wetting, polyuria, polydipsia,
polyphagia, rapid unexplained weight loss, ketoacidosis, usually
affects normal wt adults (LADA) and children
• Dx: HLA DR3/4, anti-islet, anti-GAD. At least 1 of: fasting glucose
>126 twice, random glucose >200 plus sxs, HBA1C >6.5% once, 2 hour
GTT >200 twice
– Re-test HbA1c every 3 months, goal <8% in children, <7% in adults, frequent
BP checks, heart/eye/foot exams regularly, lipid testing every 3 years, urine
microalbumin screen annually
• Tx: insulin, better to have higher glucose than lower glucose, insulin
pumps to provide continuous doses
– Aspart, lispro are short acting; detemir is long acting; glargine longest acting
 Type 2 DM
• Due to insulin resistance in peripheral tissues ultimately
leading to Beta cell failure and insulin deficiency
• Sxs: polyuria, polydipsia, polyphagia, blurry vision,
fatigue, gradual onset, truncal obesity, more genetic than
type 1
• Dx: same criteria as type 1, no antibodies. Screen adults
over 45 with HBA1c and every 3 years if <5.7%. More
frequent testing if fasting is impaired (>110 but <126)
• Tx: Want glucose between 8-120, HbA1c <7% in adults
• Complications: Nonketotic hyperosmolar hyperglycemia
 Type 2 DM
• Complications of Treatment
– Dawn phenomenon: AM hyperglycemia due to normal nocturnal release of
glucagon/epi/cortisol, increase nighttime insulin dose
– Somogyi phenomenon: AM hyperglycemia caused by nocturnal hypoglycemia and release of
same hormones as above, need to decrease nighttime insulin dose
• Acute Complications
– DKA: type 1 DM, brought on by stress/infxn/noncompliance, abdominal pain, vomiting,
acetone breath, dehydration, mental status change. Will have elevated ketones, elevated
anion gap, low pH.
– HHNK: type 2 DM, brought on by stress/infxn, causes profound dehydration, extremely high
glucose levels over 600, no acidosis, no ketones, normal pH, normal anion gap
• Chronic Complications
– Retinopathy: 3-5 years, usually neovascularization, exudate, hemorrhage
– Nephropathy: microalbuminuria that will NOT be picked up on dipstick, need a UA, tx with
ACEI or ARB, glucose/bp control
– Neuropathy: sensory and motor deficits, burning pain, foot trauma, infections, ulcers.
Autonomic nerve involvement can lead to gastroparesis, esophageal dysmotility, impotence,
orthostatic hypotension. Screen for this.
– Macrovascular: Cardiovascular disease most common cause of death. Goal bp <130/80, LDL
<100, TG <150, put patient on aspirin
 DM Treatments
• Glyburide: Sulfonylurea
– Action: increase endogenous insulin secretion
– SE: hypoglycemia, weight gain, cardiac mortality, hepatotoxic
– CI: liver or kidney disease
– Interactions: highly protein bound, careful with hypoglycemic herbs
– Gymnema has same mechanism of action
• Metformin
– Action: biguanide, inhibit gluconeogenesis in liver, increase peripheral sensitivity
to insulin, decreases intestinal glucose absorption. Very little hypoglycemia risk.
– SE: weight loss, GI upset, lactic acidosis, cardiovascular mortality
– CI: elderly, kidney disease, heart failure, liver failure
– Interactions: depletes B12, toxic with EtOH
• Troglitazone (off the market), Rosiglitazone: Thiazolidinediones
– Action: increase peripheral insulin sensitivity
– Indications: DM2 and PCOS
– SE: edema, very hepatotoxic, edema and water retention, bone loss
– CI: heart failure, fluid retention
 DM Treatments
• Insulin
– Actions: drives glucose into cells
– Indications: Type 1 and late Type 2 DM
– SE: wt gain, hypoglycemia, atrophy of injection sites
– Interactions: OCP, Thyroxine, do not combine with K
altering drugs/herbs, careful with hypoglycemic herbs
– Types:
• Short acting: with meals
– Regular: SubQ or IV 30-45 min before meals
– Lispro and Aspart have better kinetics
• Long acting: used all day long to maintain baseline insulin levels
– NPH, glargine, detemir
 DM Treatments
• Dietary: Bernstein diet (paleo), Anderson diet (low fat), 40g fiber/day, fat
under 30%
• Botanicals
– Allium, Momordica, Panax, Vaccinium (retinopathy), Gymnema
• Nutrients
– Omega 3, EPO (neuropathy)
– Fiber/flax seeds
– Vitamin C
– Vitamin D
– Niacin, B6 (neuropathy), Thiamine, biotin
– Chromium, vanadium, magnesium, potassium
– Taurine
– Bioflavonoids
– coQ10
– Glutathione, alpha lipoic acid (neuropathy)
 Metabolic Syndrome
• Sxs: Abdominal obesity, elevated bp, impaired
glucose control, dyslipidemia, gout
• Dx: 3/5
– Waist >40” men; >35” females
– TG >150
– HDL <40 men; <50 women
– BP >130/85
– Fasting glucose >100
• Tx: weight loss, control each factor by itself.
Underlying cause: insulin resistance
 Thyroid Testing
• TSH
– Elevated TSH often means that thyroid gland is not making enough T3/T4 (primary
hypothyroidism)
• Rarely, can also be a TSH secreting pituitary tumor
– Low TSH often means that thyroid gland is making too much T3/T4 (primary hyperthyroidism)
• Rarely, can also be a pituitary dysfuncion
• RAI
– Determines the distribution of iodine uptake in the thyroid tissue – only run to differentiate
hyperthyroid conditions or thyroiditis
• Total T4
– 99% bound to TBG, not really a good test, an abnormal total T4 usually only means a TBG issue
• TBG will be elevated in pregnancy, estrogen dominance, OCP use, infection, anabolic steroid use  will
show elevated total T4, but low free T4
• Free T4
– Preferred screening test. NDs also consider free T3, reverse T3
– FTI: free thyroxine index takes TBG into account
• RT3U
– How much T3 is leftover after it is bound to a bunch of TBG. Only useful for TBG questions.
– High = hyperthyroid or low TBG; Low = hypothyroid or high TBG
• T7: Only used in pregnancy because accounts for TBG alterations
 Hyperthyroidism
• Usually Graves’ disease: autoimmune, TSI antibodies
(may also have anti thyroglobulin), low TSH and high
thyroid hormones, RAI uptake high and diffuse iodine
uptake. Sxs: exopthalmos, pretibial myxedema, thyroid
bruits are specific to Graves’
• Toxic adenoma/multinodular goiter: toxic means that
they are active, RAI uptake high with scattered regions
of increased iodine uptake
• Thyroiditis (postviral/postpartum/subacute): dx based
on hx. At first, hyperthyroid as thyroid hormones are
leaked out. RAI uptake will be low because no iodine is
being taken up into the thyroid, not making any thyroid
hormones. Hypothyroid phase follows.
 Hyperthyroidism
• Sxs: weight loss, heat intolerance, anxiety, palpitations,
diarrhea, oligo/amenorrhea, insomnia
• PE: warm, moist skin, goiter, nodules, tachycardia, Afib,
tremor, lid lag, hyperreflexia
• Dx: Can only be defined by elevated T3/T4 levels, even if
TSH is normal
• DDx: anxiety, panic attack, arrhythmia, brain tumor
• Tx: propanolol, PTU, radioactive thyroid ablation
• Complications: thyroid storm s life threatening. Tx with IV
propanolol, PTU, corticosteroids, SSKI. Afib, fever, delirium.
 Hyperthyroid Medications
• Propylthiouracil (PTU)
– Actions: thyroperoxidase inhibitor so it blocks
formation of T4 and T3 in the thyroid; 5’-deiodinase
inhibitor so blocks conversion; immunosuppressive
– Interactions: hyperthyroid, thyroid storm
– SE: taste impaired, itch, hives, agranulocytosis, fatal
liver failure
– CI: liver failure, pregnancy
– Interactions: OK to use with iodine in thyroid storm
 Hyperthyroid Treatments
• Heavy metals: Mercury and Cadmium
• Nutrients: avoid iodine, high dose vitamin A
• Botanicals:
– Lycopus
– Leonurus, especially with palpitations
– Melissa
– Lithospermum
 Hypothyroidism
• Defined by low T3/T4 regardless of TSH
• Hashimoto’s thyroiditis – autoimmune, antithyroglobulin and
anti-TPO (aka anti-microsomal)
• Thyroiditis can have a hypothyroid phase that can be
permanent
• Sxs: weak, fatigue, cold, constipation, weight gain, depression,
hair loss, menorrhagia (elevated PRL), hoarse voice
• PE: dry, cold, puffy skin, bradycardia, hyporeflexia especially S1
• Tx: levothyroxine
• Complications: myxedema coma – mental status change,
hypothermia, parasympathetic sxs, need IV levothyroxine and
IV cortisone
 Hypothyroid Medications
• Levothyroxine
– Actions: Replaces T4
– SE: osteoporosis, DM worsening
• Armour
– Actions: full complement of thyroid secretions including
T3, T4, DIT, MIT
– Indications: hypothyroidism
– SE: hyperthyroidism
– CI: adrenal insufficiency, Hashimoto (can induce TPO abs)
– Interactions: OCPs because may increase TBG
 Hypothyroid Treatments
• Nutrients
– Iodine (150mcg), zinc, selenium (100 mcg max), iron
• Iodine from kelp, clams, iodized salt
– Avoid goitrogen foods (cabbage, peanuts,
strawberries, soy)
– Tyrosine
– Thyroid glandulars
• Botanicals
– Bacopa, Withania, Coleus, Commiphora, Fucus
 Thyroiditis
• Inflammation of thyroid gland
• Thyrotoxicosis followed by hypothyroidism, decreased RAI
uptake
• Can have elevation of TPO, Thyroglobulin antibodies
• Types
– Chronic lymphocytic (Hashimoto’s)
– Subacute granulomatous (de Quervain’s, postviral)
• Only type with a painful thyroid, malaise, URI sxs
– Radiation-induced
– Autoimmune
– Postpartum
– Drug-induced: amiodarone
• Tx: levothyroxine, PTU, beta blockers, NSAIDS, steroids
 Thyroid Neoplasms
• Thyroid nodules are common, more common with age, most
are benign
• Sxs: asx and discovered incidentally, can cause hyperthyroid
sxs , can cause local sxs if impinging, check for LA
– Malignant nodules: h/o radiation, cold nodules, male, young or old
age, family history thyroid cancer, rapidly growing, hoarse voice
• Dx: TFT, RAI scans. Hot nodules should not be bx, not
cancerous. US (cystic less malignant), best method is FNA.
No RAI for cold nodules. Check calcitonin levels
• Tx: radiation/surgical resection
 Thyroid Neoplasms
• Papillary
– Most common
– Slow growing
– Female dominant
– Good prognosis unless elderly
• Follicular
– Good prognosis unless elderly
• Medullary
– Found in the calcitonin producing C-Cells
– Prognosis depends on vascularity
– 80% 10 year survival rate
– Associated with MEN 2A and 2B
• Anaplastic
– Rarest
– Rapidly enlarges, rapid mets
– 10% 3 year survival rate
 Osteoporosis
• Low bone mass and microarchitecture disruption
• Risks: thin, postmenopausal women, Caucasians and Asians,
smoking, EtOH, caffeine, amenorrhea, eating disorder,
hyperthyroidism, inflammatory disease, steroid use
• Sxs: asx, can have hip fxr, vertebral compression fxr (loss of
height + kyphosis), distal radius fracture (Colles’). No bone
pain.
• Dx: DEXA T score (compared to 30 yo) -2.5 or less; Z score
(compared to same age). -1  -2.5 is osteopenia
– Run TSH, cortisol, 24-h urine Ca, CMP, SPEP/UPEP, CBC, testosterone,
vitamin D
• Tx: weight bearing exercise, Ca, Vit D, stop smoking,
bisphonates (alendronate), SERM (raloxifene)
• Complications: 50% mortality after hip fxr in 1 year
 Osteoporosis Medications
• Alendronate, Risedronate
– Actions: inhibit bone resorption by working on osteoclasts
– Indications: osteoporosis and Pagets
– SE: esophagitis, hypocalcemia, GERD
– Interactions: aspirin, estrogen
– Take away from food and stay upright
• Raloxifene
– Actions: SERM
– SE: estrogen things: DVT, embolisms, arthralgia, chest pain, rash,
migraine, edema, UTI
– CI: thromboembolisms, pregnancy, probably ER + cancers
– Interactions: protein-bound drugs
 Osteoporosis Treatments
• Botanicals
– Phytoestrogens (Trifolium, Angelica, GlycyrrhizA,
Medicago) and mineral rich (Equisetum, Urtica)
• Nutrients
– Ca, Vitamin D, Vitamin K, Mg, vitamin C, Boron,
Strontium, Silicon
• Diet
– Moderate protein, soy, low meat, low caffeine
 Paget’s
• Increased rate of bone turnover, excess resorption and
formation, mosaic pattern on xray. Viral infection.
• Sxs: asx, aching bone or joint pain, headache,
deformities, nerve entrapment, hearing loss. Skull
involvement common.
• Dxs: Increased ALP, Ca/P normal, bone scans and xray
both needed
• DDx: metastatic bone disease
• Tx: usually none, no cure, bisphosphonates, NSAIDs,
acetaminophen for pain
• Complications: fxr, high-output cardiac failure,
osteosarcoma
 Hyperparathyroidism
• Primary: usually a single adenoma, sometimes hyperplasia of PTH
gland, rarely cancerous
• Secondary: Increase in PTH to compensate for renal insufficiency
(renal osteodystrophy) because this will lead to Ca and Vit D
deficiency
• Tertiary: dialysis patients where secondary leads to hyperplasia of
the gland which now starts secreting too much PTH
• Sxs: asx, stones/bones/moans/abdominal groans/psych
overtones. Cells are less excitable when Ca is high  depressed
reflexes, neurons
• Dx: elevated ionized Ca, low P, hypercalciuria, elevated PTH, low
bone density on DEXA, might see adenoma on thyroid US
• Tx: surgery, IV fluids, loop diuretics, keep Phospate levels low
(give P binders – too much P will stimulate more PTH). Lycopus
botanical.
 Cushing’s Syndrome
• Usually iatrogenic steroid use
• Hypersecretion of ACTH more common than adrenal cause (Cushing’s
disease)
• Can also be paraneoplastic
• Sxs: htn, DM, depression (low ACTH/low endorphins), wt gain, muscle
weakness, bruising, infections, hirsutism, oligomenorrhea, striae, moon
facies, central obesity, buffalo hump, headache, hypokalemia, glycosuria
• Dx:
– Screening: 1) 24-h urine cortisol 2)midnight cortisol x2 3)dexamethasone
suppression test with AM elevated cortisol
– Measure 8AM cortisol and ACTH level to distinguish origin
– Pituitary MRI / adrenal CT
– Ectopic ACTH production will not be suppressed by high dose dexamethasone,
cortisol will stay elevated if on steroids even with dexamethasone test
• Tx: surgery followed by HRT, spironolactone
 Acromegaly
• Pituitary GH secreting adenoma
• Sxs: enlarged skull, hands, feet, facial features,
carpal tunnel sxs, sleep apnea, DM, diastolic
heart dysfunction, htn, arthritis, bitemporal
hemianopsia
• Dx: IGF-1, oral glucose suppression test (GH
stays elevated), order MRI
• Tx: surgery
 Hyperprolactinemia
• Pituitary adenoma – most common type
• Can also be caused by pituitary stalk compression,
drugs, renal failure, cirrhosis, hypothyroidism (TRH
+ PRL)
• Sxs: infertility, galactorrhea, amenorrhea (PRL
inhibits GnRH, inhibiting LH and FSH, so don’t
ovulate), vision changes
• Dx: PRL over 200
• Tx: MUST r/o pregnancy, give bromocriptine,
surgery if necessary but usually not
 Hyperprolactinemia Treatment

• Botanicals: Vitex, Lithospermum, Verbena

• Bromocriptine
– Actions: dopamine stimulator
– Indications: hyperprolactinemia, Type 2 DM,
Parkinson’s
– SE: hepatotoxic, orthostatic hypotension, can
cause cirrhosis long term
 Diabetes Insipidus
• Can’t concentrate urine because ADH is dysfunctional
• Central DI: posterior pituitary doesn’t make ADH. (tumor,
Sheehan’s, brain injury, mets, autoimmune)
• Nephrogenic: kidneys don’t respond to ADH. Causes are renal
disease, lithium use
• Sxs: polydipsia, polyuria, persistent thirst, dilute urine,
normonatremia
• Dx: water deprivation test and still excrete large volumes,
Desmopressin (ADH analog) improves central but does not improve
nephrogenic
• Tx: Central is tx with Desmopressin, Nephrogenic is treated with Na
restriction, hydration, HCTZ
 DI Treatment
• Desmopressin
– Actions: synthetic vasopressin binding receptors in
collecting ducts to increase water resorption,
stimulates vWF production
– Indications: DI, sleep apnea, Von Willebrand’s,
hemophilia, thrombocytopenia
– SE: hyponatremia, seizures
– Interactions: anything that depletes Na, careful
with adrenal herbs or diuretic herbs
 SIADH
• Euvolemic hyponatremia from excess ADH release
• Sxs: CNS disease, pulmonary disease, sarcoidosis,
COPD, paraneoplastic (small cell lung CA), drugs
(antipsychotics and antidepressants most common)
• Dx: concentrated urine, hyponatremia, patient is not
hypovolemic, elevated urine Na
• Tx: restrict fluids is most important, IV hypertonic
saline very slowly to prevent brain damage
 Adrenal Insufficiency
• Failure of glucocorticoids and mineralocorticoids to be
produced
• Primary: Addison’s disease, congenital enzyme deficiency,
Neisseria infection, TB
• Secondary: ACTH failure, usually secondary to steroid weaning
• Sxs: weak, fatigue, wt loss, anorexia, hypoglycemia,
hypotension, salt cravings, hyperpigmentation only in Addison’s
• Dx: hyponatremia and eosinophilia, hyperkalemia only if
primary cause, hypercalcemia, 8AM cortisol <3, Failure of
cortisol to rise over 18 after ACTH admin, random cortisol test
over 18 rules it out
• Tx: Steroid replacement. Addisonian crisis treated with IV
steroids, saline, dextrose, fluids
 Adrenal Insufficiency Treatments
• Nutrients
– B vitamins, especially B5
– Tyrosine, Phenylalanine
– Adrenal glandulars
– PABA potentiates cortisol
• Botanicals
– Stimulating adaptogens: Rhodiola, Glycyrrhiza,
Panax, Eleuthero, Theobroma, Coleus
 Pheochromocytoma
• Chromaffin tumor usually found in adrenal medulla or
extra-adrenal
• Highly associated with MEN 2A and 2B
• Most are adrenal origin, unilateral, bening, adult age,
sporadic
• Sxs: paroxysmal tachycardia, chest pain, palpitations,
sweating, htn, headache, tremor, anxiety
• Dx: CT/MRI adrenals. Run plasma metanephrines or
24-h urine catecholamines and metanephrines
• Tx: surgery, gives alpha blockers BEFORE beta blockers
 Hyperaldosteronism
• Excess aldosterone from zona glomerulosa of
adrenal cortex, mostly from adrenal hyperplasia,
less likely from an adenoma (Conn’s syndrome)
• Sxs: htn, HA, muscle weakness, tetany,
paresthesia, rare edema
• Dx: diastolic htn without edema, hypokalemia,
hypernatremia, metabolic alkalosis, low Mg,
hyperaldosteronism, aldosterone/renin ratio
over 30, adrenal CT/MRI
• Tx: surgery, spironolactone
 CAH
• Adrenal insufficiency due to inherited enzyme defects that
impair cortisol synthesis and result in accumulation of cortisol
precursors. ACTH elevates without cortisol, causing even more
accumulation of precursors
• 21 hydroxylase deficiency most common, can also have 11 and
17 hydroxylase deficiencies
• Can be salt-losing or non-salt-losing forms
• Sxs: females at birth with ambiguous genitals, males at birth
may have adrenal crisis (salt-losing) or precocious puberty (non-
losing)
• Dx: low Na, high K, acidosis, elevated 17-OH progesterone is
best test
• Tx: surgery, steroids
 MEN
• Tumor syndromes, autosomal dominant
• MEN 1 – Wermer’s
– PPP: pancreatic islet tumor (Zollinger-Ellison,
insulinoma, VIPoma), parathyroid hyperplasia,
pituitary adenoma
– Think about what the sxs would look like
• MEN 2 – Sipple’s
– 2A: Thyroid medullary cancer, pheochromocytoma,
parathyroid hyperplasia. RET oncogene.
– 2B: same as above + ganglioneuromatosis