Category Archives: Endocrinology and Metabolism

MOFFITT ENDOCRINE REPORT PEARLS 5/17/17: Hypercalcemia of Malignancy and PTHrP!

Hey Everyone! Thanks to Vaibhav for presenting the case of an older woman with newly diagnosed bladder cancer who presented with weight loss and failure to thrive, found to have severe hypercalcemia with workup pending. We suspected she might have PTHrP-mediated hypercalcemia, a known association with urothelial carcinomas. Pearls on PTHrP below!


Top Pearls:

  1. PTHrP is the most common cause of hypercalcemia in non-metastatic solid tumors
  2. PTHrP-related hypercalcemia is typically a finding in advanced disease with poor prognosis
  3. PTHrP acts primarily on bone and kidneys to cause hypercalcemia, not the GI tract


For those who want more info:

Check out Myung’s pearls on hypercalcemia:

*Important general pearls on hypercalcemia of malignancy: 1) It occurs in 10-30% of patients with advanced tumors. 2) It is the most common cause of hypercalcemia in the inpatient setting. 3) Prognosis is poor (up to 50% 30-day mortality).

Now some more specific info on PTHrP!

What is PTHrP?

  • Normal gene product expressed in several tissues
  • Also called humoral hypercalcemia of malignancy (HHM)
  • The most common cause of hypercalcemia in patients with non-metastatic solid tumors
  • Most often in patients with advanced disease and poor prognosis (not usually an early finding)
  • Solid tumor associations: SCC, renal/bladder, breast, ovarian
  • Liquid tumor associations: NHL, CML (blast phase), T-cell leukemia/lymphoma

How is PTHrP related to PTH?

  • First 13 N-terminal amino acids are homologous to PTH (PTH = 84 AAs, PTHrP =139-173 AAs)
  • Binds to same PTH-1 receptor as PTH: bone resorption, renal Ca reabsorption/phos wasting
  • Structural divergence after first 13 amino acids: less likely to stimulate 1,25 vit D production, does not increase intestinal Ca absorption
  • Thus, PTHrP hyperCa is from bone/renal only, while PTH hyperCa is also from GI
  • Lab findings in PTHrP hyperCa: 1) elevated PTHrP, 2) low PTH, 3) normal/low 1,25-vit D

How is measurement of PTHrP useful (aside from diagnosis)?

  • Tumor marker: helps to assess treatment response
  • Prognostic marker: worse survival if PTHrP level > 12 pmol/L, which predicts less robust response of hyperCa to bisphosphonate therapy

HyperCa Malignancy



Have a great day everyone!


Moffitt Endocrinology Report 4/19/17: Hypophysitis and Cavitary Lung Nodules

Hello Everyone!

Thank you Chloe, for presenting the case of a young woman with a history of granulomatous hypophysitis who presented with fevers and cavitary lung lesions. We discussed various entities on the ddx, including ANCA-vasculitis and lymphomatoid granulomatosis! Best,



  • Hypophysitis (or pituitary inflammation) is most frequently associated with ACTH and TSH deficiency.
  • Check out the paper on cavitary lung nodules: PMID18400799


Approach to Hypophysitis  (Inflammation of Pituitary)

  • Hypophysitis is often classified by histologic findings: lymphocytic, granulomatous, plasmacytic, and xanthomatous
  • Clinical manifestations : headache out of proportion to size of lesion, hypopituitarism : preferential hypofunction of ACTH and TSH-secreting cells have been described, but DI, hyperprolactinemia, GH excess, and autoimmune thyroiditis can also occur.
  • Eventually, progressive pituitary atrophy can occur with fibrosis.
Lymphocytic Hypophysitis Most common form; often occurs in late pregnancy or post-partum period
Granulomatous Hypophysitis Majority are idiopathic, but known causative entities include GPA and TB
Plasmacytic (IgG4-associated) Hypophysitis Often associated with infiltration of other organs, such as the pancreas
Xanthomatous Most rare, characterized by foamy histiocytes


Approach to Cavitary Lung Lesions


    • Bacteria
      • Common bacterial infections: septic pulmonary emboli, necrotizing pneumonias, lung abscess
      • Uncommon bacterial infections: actino, nocardia
    • Mycobacteria: TB and NTB
    • Fungal: aspergillosis, zygomycosis, histo, blasto, cocci, paracocci, crypto, PCP
    • Parasites: echinococcus, paragonimiasis


    • Rheum: vasculitis
    • Malignancy
    • Other: PE with infarct, bullae/cysts, pulmonary sequestration


Evernote Link:

MOFFITT AM REPORT PEARLS 3/29/17: Eosinophilia and Hypertriglyceridemia!

Hey everyone! Thanks to Evan for presenting an interesting conundrum of a young woman with abdominal symptoms who was found to have eosinophilia. We touched on a few different topics including creating a differential diagnosis for GI symptoms with eosinophilia, as well as some manifestations of hypertriglyceridemia. Pearls below!


Top Pearls:

  1. The ddx for eosinophilia and GI symptoms includes parasites, vasculitis, eosinophilic GI disease, malignancy, IBD, and primary/idiopathic hypereosinophilic syndromes.
  2. Apheresis is often indicated for triglyceride-induced acute pancreatitis. Insulin drip is 2nd line treatment.


For those who want more info:

See prior pearls below on eosinophilia definitions, ddx, and workup:

In addition, we constructed a differential for eosinophilia with GI symptoms:

  • Parasites: Strongyloides most common
  • Vasculitis: EGPA and PAN
  • Eosinophilic GI disease: esophagitis, gastroenteritis, colitis
  • Malignancy: GI lymphoma, gastric cancer, colon cancer
  • IBD: Crohn disease is a rare cause of eosinophilia
  • Primary and idiopathic hypereosinophilic syndromes: may rarely have GI symptoms


Some interesting points about hypertriglyceridemia:

Remember severe hypertriglyceridemia (TG>500) as a cause of acute pancreatitis! The risk really goes up when TG>1000.

Many patients with triglyceride-induced acute pancreatitis benefit from apheresis! If apheresis is not possible, insulin drip is recommended (with D5 infusion as needed to prevent hypoglycemia).

Hypertriglyceridemia can be caused by primary inherited disorders or by common conditions such as DM2, alcohol, hypothyroidism, pregnancy, obesity, nephrotic syndrome, renal failure, multiple myeloma, lupus, or medications. (See table below)

*HH Pearl: Hypertriglyceridemia can cause eruptive xanthomata involving tendons!




Have a great day everyone!


MOFFITT ENDOCRINE REPORT PEARLS 3/15/17: Papillary and Anaplastic Thyroid Cancer!

Thanks to Nick for presenting a case about metastatic thyroid cancer. We discussed the relationship between the papillary and anaplastic types of thyroid cancer with Mark Anderson, our endocrine report expert. Pearls below!


Top Pearls:

  1. The majority of patients with papillary thyroid cancer do not die of their disease.
  2. Most/all patients with papillary thyroid cancer need surgical resection and postoperative levothyroxine, but only higher risk patients need radioiodine therapy.
  3. Anaplastic thyroid cancer is usually a transformation from more differentiated thyroid cancer and is rapidly fatal.


For those who want more info:

Papillary Thyroid Cancer:

Risk Factors: Childhood radiation exposure (e.g. dental radiation before we had lead thyroid shields!) and family history of thyroid cancer.

Presentation: A thyroid nodule noted by the patient, physician, or incidental radiologic finding. Size of the tumor, older age at diagnosis, histological subtype, and presence of invasion or metastasis are the main features associated with worse morbidity and mortality. <10% of patients have metastases beyond the neck at the time of diagnosis (2/3 are pulmonary, 1/4 are skeletal).

Prognosis: Most patients with papillary thyroid cancer do not die of their disease (only ~5% cancer-related mortality over 15 years).

Treatment: All patients should have surgical resection including part or all of the thyroid gland, depending on extent of disease. Postoperatively, patients are stratified based on risk factors for persistent/recurrent disease. Most patients require postoperative levothyroxine (T4) to suppress TSH (TSH goal depends on risk stratification). Higher risk patients also receive postoperative radioiodine. Surveillance includes neck ultrasound, TSH, and serum thyroglobulin (Tg) levels to detect recurrent disease.


Anaplastic Thyroid Cancer:

Presentation: Rapidly enlarging neck mass. 20% have a history of differentiated thyroid cancer, which is often present concurrently!

Differential diagnosis: poorly differentiated thyroid cancer, lymphoma, melanoma, and sarcoma.

Prognosis: Nearly always rapidly fatal.

Treatment: Complete surgical resection with postoperative chemoradiation, or chemoradiation alone if disease is inoperable. Commonly used agents are doxorubicin, docetaxel, and cisplatin. Clinical trial enrollment and concurrent palliative care are recommended.

*Pearl: All anaplastic carcinomas are considered stage IV, regardless of the extent of disease!

Transformation: Anaplastic thyroid cancer usually arises from transformation of a differentiated thyroid cancer, though it can occur de novo. Transformation typically occurs in the thyroid or cervical lymph nodes, but may rarely occur at metastatic sites.




Have a great day everyone!




MOFFITT ENDOCRINE REPORT PEARLS 1/25/17: Hyponatremia and the DDAVP Clamp!

Thanks to Sam for presenting the case of a middle-aged man found down with hyponatremia and hypoglycemia that resolved with IV fluids and other supportive measures. Sam taught us a bit about preventing overcorrection of hyponatremia with DDAVP (affectionately known as the “DDAVP clamp”)! Pearls below:


Top Pearls:

  1. Hypertonic saline is the tx of choice for acute hyponatremia and chronic symptomatic hyponatremia.
  2. DDAVP “clamp” may be used for severe chronic symptomatic hyponatremia (co-administration of hypertonic saline and desmopressin) to prevent overcorrection.
  3. Do not use DDAVP in psychotic patients, edematous patients, or chronic SIADH.


For those who want more info:

Hyponatremia is acute if it is known to have occurred within 48 hours. If >48 hours or unknown, it is chronic.

The recommended correction is no more than 8 mEq/L/day. This applies to both acute and chronic hyponatremia, although the risk of demyelination is less with acute hyponatremia.

*Pearl: Thanks Lauren for letting us know that the term “central pontine myelinolysis” has been replaced with “osmotic demyelination” since it occurs outside the pons as well!

Most cases of osmotic demyelination occur in severe hyponatremia (Na <120) when the rate of correction was more than 10-12 mEq/L in 24 hours.

Therapy regimens:

Emergency therapy = hypertonic saline bolus, 50-100 mL over 10-15 mins. Indicated in patients with severe symptoms (seizures, obtundation) and acute symptomatic hyponatremia (even mild symptoms!).

Non-emergency therapy = hypertonic saline infusion, 15-30 mL/hour. Indicated in patients with severe hyponatremia (Na <120) with mild symptoms, and acute asymptomatic hyponatremia.

What about isotonic saline? Primarily used for correction in mild hypovolemic hyponatremia (Na >120) with minimal or no symptoms. Make sure to look for causes that might be better treated with free water restriction or disease-directed therapy (e.g. steroids for adrenal insufficiency).

Sam Miller taught us about the “DDAVP clamp”: co-administration of hypertonic saline and DDAVP to prevent overly rapid correction of sodium levels. It can be considered in severe chronic hyponatremia but less in acute hyponatremia since the risks of overcorrection in that setting are lower.

The “clamp” regimen is a slow infusion of hypertonic saline (15-30 mL/hour) in combination with desmopressin (1-2 mcg IV/subQ) every 8 hours for 24-48 hours.

If DDAVP is used, it is important to restrict subsequent free water intake to avoid worsening hyponatremia. It also should not be used in psychotic patients, edematous patients, or chronic SIADH.



Have a great day everyone!



MOFFITT ENDOCRINE REPORT PEARLS 1/11/17: Thyroid Storm and Coarctation of the Aorta!

Thanks to Arielle and Sam for sharing the case of a woman with thyroid storm, and also to Laura for showing an image for a young man with refractory hypertension found to have coarctation of the aorta!


Top Pearls:

  1. Thyroid storm is a clinical diagnosis based on the following factors: 1) Temperature 2) CNS effects 3) GI/hepatic dysfunction 4) Tachycardia/a-fib 5) Heart failure 6) Precipitant history.
  2. There is typically an underlying cause (Graves most common) and a precipitating event (e.g. surgery, infection, or iodine exposure).
  3. Thyroid storm has high mortality (20-30%)!


For those who want more info:

See these prior Moffitt pearls about thyroid storm:

*Pearl: As Arielle reminded us, a cause of thyroid storm is the withdrawal of a thyroid suppressing medication, such as lithium!


Coarctation (narrowing) of the aorta:

  • Location: typically at ductus arteriosus insertion point just distal to left subclavian artery
  • Sequelae: HTN and LV overload (LVH)
  • Epidemiology: M>F (59%)
  • Genetics: Most cases are congenital (present at birth), and there is a suggestion of genetic predisposition, but can be acquired (e.g. Takayasu arteritis)
  • Associations: Turner syndrome, bicuspid aortic valve, VSD, PDA, intracranial aneurysms
  • Natural history: Average survival of 35 years without treatment!
  • Causes of death: Heart failure, aortic rupture/dissection, endocarditis, ICH, MI, arrhythmias
  • Physical exam:
  • *Lower extremity SBP < Upper extremity SBP*
  • *Radial artery to femoral artery pulse delay*
    • Rarely, the coarct is above one or both subclavians, so BPs may differ or all be the same!
    • Continuous heart murmurs due to large collaterals
    • Systolic click from bicuspid valve
  • Notched ribs due to enlarged intercostal vessels (thanks Harry for the Xray!)


  • Echo with complementary CT/MRI is diagnostic (CT reconstruction below):


  • Treatment: For adults, transcatheter intervention with stenting is the preferred approach, indicated in patients with high gradient or imaging evidence of significant coarctation with collateral flow.



Have a great day everyone!




Moffitt AM Report 10/26/16: Adrenal Insufficiency, Hyperthyroidism, and Methimazole-induced Agranulocytosis!

We had a great Endocrinology morning conference today with 2 endocrine cases that were presented:
1) A case of an elderly man on high dose steroids who presented with hypothermia and bradycardia, with concern for adrenal insufficiency.
2) A case of a young woman with Graves Disease who presented with agranulocytosis secondary to methimazole.


  • Dexamethasone can rapidly suppress the hypothalamic-pituitary-adrenal axis and also has a long half-life. Hence, it often limits interpretability of cort-stim test results. Hence, we tend to preferentially use hydrocortisone for stress-dose steroids in our inpatients.
  •  Agranulocytosis is a rare (prevalence of 0.1 – 0.5%) but serious complication of methimazole use. When starting patients on this therapy, always counsel them for infectious signs or symptoms.
  • See below for a cool flow-chart for approaching hyperthyroidism.

Approach to Hyperthyroidism

  • Useful question to ask when a patient has a low TSH is the presence of neck pain or discomfort. If painful – consider thyroiditis (subacute , infectious, radiation, trauma-induced) as an etiology! But note that there are causes of painless thyroiditis as well.
  • An older pearl, but we LOVE this diagram of approaching hyperthyroidism:


Methimazole-induced Agranulocytosis

  • Remember, a number of meds can cause agranulocytosis. Most common agents are: clozapine, thionamides (eg methiamzole), sulfasalazine, ticlodipine.
  • Prevalence ranges from 0.2 – 0.5%
  • PTU (another anti-thyroid med) can also cause agranulocytosis. Note, methimazole-related agranulocytosis is dose-dependent (higher risk in patients taking >40 mg/day), whereas PTU-related agranulocytosis is dose-independent!
  • Mechanism of agranulocytosis in methimazole is likely multifactorial, with a component of 1) direct toxic effect on marrow granulocytic precursors; and 2) immune mediated destruction of circulating neutrophils by drug-dependent or drug-induced antibodies.
  • The benefit of monitoring patients on thionamides for development of agranulocytosis is uncertain. Hence, the general approach is strict return precautions – advise patients to have a WBC with differential at the earliest sign of a sore throat or other infection, and to discontinue the drug until the result is available.
  • Treatment: 1) Withdrawal of offending agent
    2) Treatment of associated infection
    3) GCSF: efficacy is not conclusively proven, but several case non-randomized studies have reported excellent benefit.