Endocrinology and Metabolism Referral Guidelines

1. Obesity— PCM should refer the patient for obesity if there is evidence supportive of an underlying endocrine disorder. Endocrine disorders which are associated with obesity are Cushing’s syndrome, poorly controlled thyroid disease, hypogonadism, PCO, growth hormone deficiency and very rarely hypothalamic dysfunction.
   • PCM should treat hypothyroidism and reassess weight after thyroid function has normalized for at least 6 months. Referral is not required for hypothyroid-associated weight issues in euthyroid individuals or untreated hypothyroid patients.
   • Consider referral for nutrition consult in all obese patients; utilize LEAN program as appropriate.
   • Active Duty prediabetics should be referred to prevent progression to diabetes.
   • Consider medications as a factor in weight gain.
   • Screen selected patients with 24hr Urine Free Cortisol/Cr and TSH prior to routine endocrine referral.


2. Hypothyroidism—TSH > upper limit of normal is a very common problem. Hashimoto’s thyroiditis is the most common cause of hypothyroidism in the developed world and does not require subspecialty consultation. Hypothyroidism is defined as an elevated TSH with a low FT4. Subclinical hypothyroidism is an elevated TSH and normal FT4. There is clear-cut benefit to treating hypothyroidism in all patients and patients with subclinical hypothyroidism with a TSH > 10.
   • Check TSH, FT4 and TPO Antibodies.
   • IF TSH > 10 consider starting levothyroxine and titrating to a TSH < 3 but > lower limit of normal.
   • If TSH > 5 and TPO Ab+, consider starting levothyroxine as these patients have a 2% risk/yr of developing hypothyroidism.
   • TSH and FT4 should be checked no sooner than 6-8 weeks after initiation or making a change in thyroid hormone doses.
   • In patients with mild hypothyroidism (TSH < 10), Levothyroxine can be started at 25mcg once daily and titrated upward to a normal TSH every 6-8 weeks.
   • In younger patients with overt hypothyroidism (TSH > 20 with low FT4) levothryoxine can be started at 75 to 100mcg daily (or 1.6mcg/kg body weight) and titrated every 6-8 weeks to a normal TSH range.
   • In elderly patients or those with underlying cardiac disease levothyroxine replacement should be started LOW and increased SLOWLY to avoid adverse cardiac effects. I.e. levothryoixine 25mcg daily increased by 25mcg every 8-12 weeks until goal TSH is reached.
   • Symptoms of hypothyroidism are very non-specific and many patients do not have change in symptoms with correction of TSH. The PCM should then presume that the symptoms are unrelated to thyroid function and referral is not required.
   • Patients should take thyroid hormone on an empty stomach, and not with calcium containing products, iron, or antacids.
   • If a woman is started on oral contraceptives or estrogen replacement, her thyroid hormone requirements will increase and her TFT’s should be reassessed in 2-3 months. If a woman stops her OCP’s or estrogens, her thyroid hormone requirements will decrease and her labs should be reassessed in 2-3 months.
   • Pregnant women on levothyroxine should have thyroid function checked after pregnancy is confirmed and again 4 to 6 weeks afterwards, with goal TSH lower limit of normal to 2.5 throughout pregnancy. Increases in doses of levothyroxine by up to 25% are usually required in pregnancy. Hypothyroidism in pregnant patients is to be avoided. For any concerns in this patient group early referral to OBgyn or endocrine is appropriate.
   • Refer patients with hypothyroidism if the PCM is unable to maintain the TSH in a normal range with the above-mentioned manipulations (Routine consult).


3. Hyperthyroidism—Subclinical hyperthyroidism is defined by ‘suppressed’ TSH (< 0.1) and normal FT4/T3. Hyperthyroidism is defined as suppressed TSH with elevated FT4 or T3. Hyperthyroidism can be caused by autoimmune thyroiditis (Graves’ Disease, painless thyroiditis or Hashimoto’s thyroiditis), toxic nodules, subacute thyroiditis and exogenous thyroid hormone. The majority of these patients are managed on a Routine basis. Patients with “depressed” TSH in range of 0.1-0.3 do not require endocrine consultation unless there are symptoms of hyperthyroidism or structural abnormalities on physical exam to include goiter or nodules. Elderly patients with low TSH (< 0.3) who have low bone mass/osteoporosis or underlying cardiac disease should be considered for treatment.
   • If the patient is on thyroid hormone, reduce the dose and titrate until TSH is in the normal range.
   • Consider thyroid uptake and scan for overt hyperthyroidism (TSH < 0.015) unless clear cut thyroiditis (do not need these studies if thyroiditis strongly favored).
   • Routine consultation to Endocrinology is appropriate for any persistently suppressed TSH < 0.015. If the patient is frankly thyrotoxic (tachycardia, tremor, large weight loss), please call Endocrinology to arrange a 72 hour consult and facilitate RAIU/SCAN testing.
   • Start Atenolol or Inderal and titrate for resting P< 90bpm pending Endocrinology evaluation if no contraindications to beta blockers for overt thyrotoxic patients.


4. Thyroid Nodules— are found in > 50% women over age 50. They are more likely to be concerning if found in children, the elderly and in men.
   • Check TSH. If TSH is suppressed, follow hyperthyroidism guideline for a Routine consult.
   • If the nodule is found incidentally during radiographic evaluation of other organ systems, send a Routine consult if the nodule is > 1 cm or is described to have concerning characteristics. If < 1 cm or entirely cystic (simple cyst) no f/u is warranted.
   • If the nodule is found on palpation send a Routine consult.
   • All thyroid nodules discovered on PET scanning should have a Routine consult placed.


5. Thyroid cancer— All thyroid cancer should be referred to Endocrinology for follow-up (Routine).
   • Check TSH and thyroglobulin, thyroglobulin antibodies.
   • Assure patient has original pathology results and all notes pertaining to their prior therapy with them at their appointments.


6. Diabetes Mellitus— The PCM is asked to manage all diabetics during their routine visits. Please use the appropriate Family Practice physicians and Internists to assist in managing the urgent and routine needs of Diabetics in your population. Quarterly assessment of HbA1c (goal < 7%), bi-annual assessment of lipids (goal LDL < 100), and annual assessment of renal function (microablumin and Cr) and ophthalmology exam are expected to be ordered and assessed by the PCM. Referral to Podiatry and Nephrology as required should be initiated after examination by the PCM. Additional assistance in managing complex patients with poor control can be obtained via the Diabetes Clinic via Routine consult.
   • All new Diabetics should be referred to Diabetes Education and Diabetes Nutrition classes.
   • All diabetic should be using a glucometer to check, at a minimum, fasting blood sugars.
   • Type 1 Diabetics can be referred to Endocrinology if Internal Medicine clinicians are unavailable.
   • All insulin pump users should be referred for a Routine consult to Endocrinology or Diabetic Clinic.
   • Any poorly controlled Type 2 Diabetics may be referred to the Diabetes Clinic (Routine).


7. Hypoglycemia— Any patient with unexplained fasting or postprandial hypoglycemia should be evaluated with labs before referral unless there are signs of neuroglycopenia (altered mental status or seizures). Patients with hypoglycemia should fulfill Whipple’s triad: symptoms, documented concurrent hypoglycemia, and resolution with eating.
   • Refer to Internal Medicine with admission if there are any concerns for neuroglycopenia that require supervised fasting.
   • Check fasting AM glucose, insulin, and c-peptide.
   • Check glucose, insulin, c-peptide, proinsulin and urine sulfonylurea if patient is seen with symptoms.


8. PCOS— around 10% of reproductive-aged women have PCO as defined by the Rotterdam criteria which is 2/3 of the following criteria: polycystic ovaries on imaging, oligomennorhea, and clinical or biochemical signs of hyperandrogenism with no other underlying cause. These individuals, once diagnosed, can be managed by their PCM and/or OB-gyn. First line treatment is lifestyle changes to diet and exercise to promote 5 to 7% body weight reduction (referral to LEAN program may be appropriate). Treat with OCP’s to force cycles at least quarterly. Metformin use may restore ovulation, decrease weight, and improve insulin resistance in some individuals. These patients are at a higher life time risk for cardiac disease and should be managed accordingly (strict BP, lipid, weight, BG control)
   • Measure testosterone, DHEAS, prolactin, 17-OH progesterone (follicular phase, 0800am) + progesterone, LH/FSH and TSH.
   • Refer to Ob-gyn or Endocrine for Routine consult if there is a question about the initial diagnosis.
   • Once placed on medications for management, the patient may return to the PCM for continued care as these medications are meant to be chronic. Please contact the consulting provider if further questions remain about ongoing care.


9. Hirsutism— defined as excess body hair in male-pattern areas including face, chin, neck, nipples, pelvis, abdomen, and legs. Evaluation should rule out underlying causes of hormonal disequilibrium, with the most common reasons being idiopathic, familial and PCOS. Evaluation for signs of virilization by the PCM or Ob-gyn is appropriate and is considered a high risk feature.
   • Measure testosterone, DHEAS, prolactin, 17-OH progesterone (follicular phase, 0800am) and TSH.
   • Refer to Endocrine for a Routine consultation for assistance with diagnostic evaluation and recommendations on therapy.


10. Hypercalcemia— defined as corrected Calcium above the upper limit of normal or elevated ionized calcium. All Calcium labs should be performed with a concomitant albumin. (The correction for Calcium is to add 0.8 for every point albumin is below 4, and subtract 0.8 for every 1 point that albumin is above 4). If the patient has symptomatic hypercalcemia, the patient should be managed as an inpatient. If the patient is asymptomatic, an outpatient evaluation should ensue.
    • Lab evaluation: 24 hr Urine for calcium+creatinine+sodium, renal panel (Ca, phosphate, creatinine, alkaline phos., albumin), ionized Calcium, PTH, 1,25 vitamin D, SPEP/UPEP (if over age 40), TSH, PTHrp and urinalysis
    • If PTH is not suppressed to lower-limit of normal and Calcium is elevated, refer to endocrinology as a Routine consult.
      • consider ordering a DXA scan
    • If PTH is suppressed to the lower limit of normal, or other causes are noted, please consider referral to Internal as a Routine consult.


11. Osteoporosis— defined as t-score <2.5 in a postmenopausal woman or man > 50 yo or a non-traumatic fragility fracture. DXA should be ordered in any postmenopausal woman and in anyone with risk factors that would increase possibility of fracture. This includes hypogonadism, alcoholism, chronic glucocorticoid use, and anorexia/wt < 120 lbs in women, recurrent fragility fractures, family h/o osteoporosis in a first-degree relative and hyperparathyroidism. Men <50 and premenopausal women cannot be defined as osteoporotic but are characterized as low bone mass for age/sex. The decision to treat low bone mass (z-scores <2 SD below peers) should be made as a decision between patients and their PCM. All patients could benefit from an intake of 1000-1500 mg Calcium daily and 1000 IU vitamin D.
    • Assure DXA scan has been performed prior to consultation and if one has been done on island prior, that the repeat is performed at the same facility/same machine.
    • Evaluation for secondary causes of osteoporosis includes h/o above risk factors, 24hr urine for calcium and free cortisol, renal panel, PTH, calcidiol, tsh, testosterone (men), menstrual hx.
    • Routine consultation to endocrine for treatment recommendations for secondary causes of osteoporosis or difficulties with osteoporosis therapy management.
    • Routine consultation for men with unexplained low bone mass for age is appropriate for a secondary workup.
    • DXA scans should not be performed for evaluation of activity-induced stress fractures (ie boot camp stress fractures).


12. Hypertension— evaluation for secondary sources of Endocrine HTN include ruling out Cushing’s, Primary Hyperaldosteronism or Pheochromocytoma. Many common medications and as well as withdrawal from certain drugs can adversely affect screening tests. It is beyond the scope of these guidelines to list all contributors and the reader is directed to any reputable internal medicine reference or website for complete screening instructions or they may contact the endocrine clinic for questions.
    • Check plasma free metanephrines.
    • Check AM rennin (PRA), aldosterone (PAC), and renal panel to screen for renin mediated hypertension or primary hyperaldosteronism.
    • Check 24 hr Urine Free Cortisol with creatinine or 0800 AM Cortisol after 1 mg oral Dexamethasone the previous night at 11 pm(1 mg DST).


13. Fatigue (r/o Adrenal Insufficiency)— Adrenal Insufficiency can present in an otherwise asymptomatic patient when they encounter physical stressors. An appropriate evaluation includes an AM random cortisol and renal panel. Coexisting autoimmune disease make this more likely. Accompanying weight loss, hyperkalemia, orthostasis, nausea or emesis and abdominal pain, or inappropriate tan/darkening of hand creases or scars increase likelihood of diagnosis.
    • Check AM unstressed fasting cortisol. If cortisol <3, AI very likely. If cortisol > 10, AI unlikely. For cortisol >3 but <10, consider ACTH stimulation testing (Draw baseline cortisol and give 250mcg cosyntropin Im or IV; drawm cortisol at 30 and 60”. Increase in cortisol should be >10 or total >18.)
    • Routine referral for ACTH stimulation testing and evaluation should follow ruling out other causes of fatigue (check TFT’s, CBC, and fasting BG, treat volume depletion.)


14. Post-Gastric Bypass— patients who have undergone Gastric bypass require ongoing evaluation for malabsorption and vitamin deficiency. If they are not receiving this care from their bariatric surgery center, please evaluate the following and refer if they have issues. All Gastric bypass patients should be on MVI’s daily.
    • All Gastric bypass patients should be referred to the TAMC bariatric surgery center for ongoing care.
    • Iron panel, vitamin B12, folate, vitamin D, vitamin A, carotene, renal panel and PTH.
    • Routine referral for abnormalities.


15. Adrenal Incidentaloma— present in 10% of the population. Evaluation of these include obtaining the following labs with follow-on referral to Endocrinology (routine)
    • Metanephrines (24 hr urine), DHEAS, renal panel, 24hr urine free cortisol (or 1 mg overnight DST –see Cushing’s below), aldosterone and plasma renin activity.
    • If mass > 4.0 cm, call Endocrine for more urgent referral.
    • Do not order FNA of adrenal mass prior to ruling out pheochromocytoma.


16. r/o Cushing's Syndrome— Evaluate appropriate patients which include those with centripetal obesity pattern, easy bruising, recurrent fungal/skin infections, rapid new weight gain or difficult to control hypertension, purple striae, proximal muscle weakness, or unexplained hypokalemia.
    • Repeated 24hr urine free cortisols (UFC) or overnight dexamethasone suppression testing DST (give 1 mg po dexamethsaone at 2300 then obtain 0800 fasting serum cortisol—patient must sleep overnight).
    • Contact or refer to Endocrine for abnormal screens (abnormal tests: 1 mg DST AM cortisol> 5 ug% or 24 hour urine cortisol x2 ULN).


17. Known Pituitary Disease— Any patient with history of known pituitary dysfunction or hyperfunction, or pituitary tumors, should be followed by Endocrinology with routine referral.
    • Pituitary apoplexy should be a today consult as should any question of frank pituitary failure or diabetes insipidus when the patient appears unstable or is frankly symptomatic.
    • If known pituitary problems have been defined, screening for current status with fasting am labs is helpful (LH/FSH, cortisol, prolactin, TSH, FT4, IGF-1, cortisol, testosterone (if male)).


18. Pituitary Incidentaloma— Pt with incidentally discovered pituitary adenomas, including those without symptoms of hormone dysfunction, should undergo clinical and laboratory evaluation for hormone hyper and hypo secretion with follow on referral to endocrinology. If initially seen on other imaging modality a MRI of the sella with GAD should be ordered to better delineate the nature and extent of the incidentaloma.
    • Pituitary incidentalomas are a routine endocrine referral.
    • Adenomas should be screened with prolactin, IGF-1, TSH/FT4, FSH/LH, testosterone (if male) and baseline AM cortisol followed by 1mg overnight DST and ACTH level if Cushing’s disease is suspected (see 13 and 16 above).
    • All patients with adenomas abutting the optic nerves or chiasm on MRI need a formal visual field exam and same day referral to Endocrine and Neurosurgery.
    • Concerns for pituitary apoplexy should be addressed as in 17 above.


19. Traumatic Brain Injury (TBI) – TBI can be associated with neuro-endocrine dysfunction (NED). Clinician confirmed or patient reported TBI that includes ANY ONE of the following may be at risk for NED due to TBI: 1) 24 hour hospitalization post injury 2) abnormal imaging post injury with symptoms suggestive of NED 3) persistent TBI symptoms at 3 to 6 months post injury. Symptoms of NED include depression, cognitive impairment and/or emotional liability and findings suggestive of pituitary dysfunction such as hypogonadism, growth hormone deficiency, hypothyroidism, hyperprolacinemia, adrenal insufficiency.
    • Routine screening labs (drawn at 0800): cortisol, testosterone (male),LH, FSH, prolactin, Igf-1, TSH and FT4.
    • If abnormal screening then routine referral to endocrinology is appropriate.


20. Polyuria/Polydipsia- Can be caused by Diabetes Insipidus, Psychogenic Polydipsia, hypercalcemia and poorly controlled diabetes mellitus. If patients do not have frank DM, Hypercalcemia, or Pschyogenic Polydipsia they should complete a 24 hour urine collection for total volume, creatinine, urine osmolarity with simultaneous serum osmolarity and full chemistries. Screening Urinalysis of a patient with DI is expected to have low specific gravity. If specific gravity is high, look for other causes.
    • Screen for Diabetes Mellitus and hypercalcemia.
    • Rule out psychogenic polydipsia by history, if possible.
    • Collect 24 hr Urine creatinine with total volume, osmolality (urine and serum simultaneously), and concurrent renal panel (full chemistry panel).
    • Routine referral to Endocrine for high volume polyuria not due to DM.
    • Consider Internal Medicine inpatient admission for evaluation of patients who are symptomatic or who have serum sodium levels >149 or <125.


21. Hyponatremia- Any patient with unexplained hyponatremia should have been screened with laboratories before being referred for SIADH. SIADH is a diagnosis of exclusion when the patient is euvolemic and other causes have been assessed and ruled out.
    • Consider effect of medications.
    • Screening AM cortisol, TSH/Free T4, plasma and urine osmolarity, urine electrolytes, and plasma osmolarity and complete chemistries.


22. Gynecomastia- refers to male breast enlargement due to proliferation of glandular and stromal tissue. 30% of men older than 40 years have some palpable breast tissue. Concerning findings include unusual firmness, a fixed mass, bloody nipple discharge, ulceration and local adenopathy. Recent or symptomatic gynecomastia is more likely to be clinically important and requires further evaluation.
    • Consider thorough drug and medical history.
    • Testicle exam for size and masses.
    • Screening labs bHCG, DHEAS, Total Testosterone, FSH, estradiol, prolactin, TSH/FT4.
    • Routine referral to endocrine if hormonal cause is in question or treatment is desired.


23. Male Hypogonadism- androgen deficiency can result from abnormal testicular function (primary disease manifested by elevated FSH/LH with low T) or abnormal hypothalamic/pituitary regulation of testicular function (secondary disease with low or inappropriately normal FSH/LH in response to a low T). Symptoms include reduced libido, decreased spontaneous erections, loss of body hair, infertility, reduced muscle strength, hot flushes and sweats, small or shrinking testes, and breast enlargement or tenderness. Less-specific symptoms include decreased energy, motivation, initiative, depressed mood and poor concentration and memory.
    • General health evaluation, testicular exam, exclude illness, trauma history, eating d.o, and drugs (marijuana, etoh, anabolic steroids, cocaine).
    • 0700-0800hrs Total Testosterone (T) – repeated at least 2-3 times over 1-2 months to confirm low value (T<250 lower limit of normal using the TAMC reference range, which is calibrated to the local population ).
    • After confirmation of low values repeat Testosterone with FSH/LH to determine primary vs secondary.
    • Primary disease (elevated LH/FSH) – routine referral to urology.
    • For secondary disease (low or inappropriately normal LH/FSH) consider recreational drug use, obstructive sleep apnea, chronic diseases (liver, CKD, CHF), TBI hx and obesity. Lab evaluation includes serum prolactin, iron and ferritin, CBC, LFTs and PSA. Consider a MRI of sella to r/o a space occupying lesion.
    • Routine referral to endocrine for secondary hypogonadism evaluation and initiation of treatment is appropriate.


24. Hyperprolactinemia- signs of elevated prolactin (PRL) include infertility, amenorrhea, and galactorrhea. If due to an expanding pituitary lesion symptoms could include headache, visual field defects or ophthalmoplegia. Secondary hypogonadism can be seen in men and women with high PRL. Patients discovered to have high PRL levels should be screened for medications that cause PRL elevations (D2 Dopamine receptor antagonists); signs/symptoms of hypothyroidism, renal disease and cirrhosis; and screened for headache or visual symptoms. PRL levels should be checked after an overnight fast. Patients should avoid sexual activity, chest wall/nipple stimulation, excessive exercise and very high carbohydrate meals 24 hours prior to testing. Mildly elevated PRL levels are common and all elevated values should be verified by repeat analysis.
    • Check TSH to r/o hypothyroidism and HCG to r/o pregnancy in premenopausal females.
    • PRL levels over 200mg/ml are highly indicative of a macroprolactinoma.
    • If there is no obvious cause for an elevated PRL a MRI of sella with GAD is indicated.
    • Symptoms due to an elevated PRL or findings suggestive of an adenoma on MRI are an indication for a routine referral to endocrine.
    • Mild PRL elevations (25-50ng/ml) can cause infertility even in premenopausal women with normal cycles.