Category Archives: Endocrinology and Metabolism

VA Ambulatory Report 9.13.17 – Vitiligo, Hashimoto’s, and Pernicious Anemia

Thank you to Rabih for presenting this interested case of a young man presenting to clinic with fatigue, weight gain, hypopigmented skin lesions found to have pernicious anemia, hashimoto’s and possible vitiligo.

Key Learning Points

  • For skin hypopigmentation try to determine if there is complete depigmentation vs. hypopigmentation to narrow your differential
  • Decision to treat subclinical hypothyroidism is based on level of TSH elevation, age, CV risk factors, and symptoms
  • Consider pernicious anemia as a cause of B12 deficiency especially in patients with other autoimmune diseases


Hypopigmentation of the skin

  • First try to determine if it is complete depigmentation or hypopigmentation.  This can be difficult especially in lighter skin individuals.
    • Degpimentation
      • Vitiligo – most frequent cause of depigmentation
        • Loss of epidermal melanocytes
        • Etiology not known, but associated with autoimmune diseases
        • No racial or ethnic propensity but often causing more impact on darker skin individuals due to is being more disfiguring
      • Consider exposures to chemicals (such as those found in hair dyes, insecticides, adhesives) or meds (topical steroids, imatinib, pegylated interferon)
    • Hypopigmentation
      • Commonly seen after an inflammatory skin process
      • Infections – pityriasis versicolor, leprosy, syphilis, non-syphilis treponema, onchocerciasis
      • Atopic – pityriasis alba
      • Rheumatologic causes – scleroderma, discoid lupus
      • Acquired
        • idiopathic guttate hypomelanosis – seen with aging
        • progressive macular hypomelanosis – unknown cause, possibly related to infection, typically seen in young adults, more common in darker skin individuals
      • Nutritional deficiencies – B12, copper, iron, kwashiorkor
      • Endocrinopathies – hypopituitarism, Cushing syndrome,


Subclinical Hypothyroidism

  • Definition: Elevated TSH with Normal T4
    • Always recheck after 2-3 months given these are numbers are dynamic to confirm subclinical hypothyroidism
  • When should we treat subclinical hypothyroidism? Based on TSH level, age, symptoms, TPO antibody status, and CV risk factors
    • TSH >10
      • Treat all patients <70
      • For patients >70 only treat if symptoms are present or have +TPO antibody
    • TSH 7-10
      • If symptoms are present
      • If patient is <70 and has cardiac risk factors or has +TPO
        • Patients who are younger and have +TPO antibodies are more likely to progress to overt hypothyroidism
    • TSH 4-7 AND
      • Symptoms of hypothyroidism: consider 6 month trial of treatment but stop therapy is symptoms do not improve with treatment
  • See this discussion in NEJM for more review of subclinical hypothyroidism
  • Recent study in NEJM showed no benefit to treating subclinical hypothyroidism in adult s> 65 years


Pernicious Anemia Fun Facts

  • What is pernicious anemia? Anemia due to autoimmune atrophic gastritis.
    • Autoanitbodies to intrinsic factor and parietal cells –> Loss of parietal cell mass –> hypochlorhydria and inadequate production of intrinsic factor –> B12 malabsorption –> anemia
  • It is called pernicious anemia because when it was described patients symptoms would progress gradually over time without available treatment
  • Diagnosis
    • Macrocytic anemia, low B12
    • Autoantibodies to parietal cells and intrinsic factor
      • Antibodies to IF are specific but not sensitive
      • Antibodies to parietal cells have better sensitivity, but only ~80%
      • If high enough concern and negative antibodies, may need EGD with biopsy demonstrating atrophic gastritis in the gastric body
    • Can also check serum gastrin which will be elevated
  • 40% of patients will have autoimmune thyroid disease
  • There is a theory that H. pylori infection may trigger the autoimmune destruction of parietal cells. However patients with pernicious anemia are less likely than age matched controls to have h. pylori. Associated with H. pylori infection thought possibly due to active infection gradually replaced by an autoimmune process
  • Increased risk of gastric neuroendocrine tumors and adenocarcinoma

SFPC Ambulatory Report 7.13.17 Post-pancreatectomy diabetes

Thanks to Alicia for presenting a challenging management case of a patient with ESRD s/p transplant and traumatic pancreatectomy resulting in brittle diabetes.
Learning Pearls
  • Post-pancreatectomy considerations
    • Reasons people lose pancreatic function
      • Diseases: CF, chronic pancreatitis
      • Surgical resection due to malignancy, trauma, chronic pancreatitis
    • Endocrine replacement
      • Insulin: Patients should be treated similar to those with Type 1 Diabetes
      • Patients also lose their endogenous glucagon production
    • Exocrine replacement
      • Pancreatic enzymes
      • Vitamin supplementation: Should also supplement with the fat soluble vitamins (Vitamins A, D, E, K) due to fat malabsorption
  • Insulin pump Criteria
    • American Association of Clinical Endocrinologist recommendations for the Ideal candidates in adult patients:
      • DM type 1 or DM type 2 who is insulin dependent and intensively managed
      • Performing >= 4 insulin injections and >=4 glucose checks daily
      • Motivated
      • Willing and able to carry out the necessary tasks to manage the pump
      • Willing to maintain frequent contact with the healthcare team
        • Multidisciplinary team follow-up including pump trainer, educator, and endocrinologist
        • Monthly specialist f/u until on stable regimen
  • Islet cell/pancreas transplant
    • Can isolate islet cells from a resected pancreas or transplant full pancreas
    • ~30% of patients are insulin free after islet cell transplant.  Success depends on the mass and quantity of islet cells transplanted
    • Require lifelong immunosuppression therefore you will need to balance the risk of immunosuppressive medications with the benefits
    • ADA criteria for transplant:
      • Patients with ESRD who have had or will have a kidney transplant.  Most often perform simultaneous pancreas-kidney transplant
      • Patients without renal disease who have a history of severe metabolic complications from DM and consistent failure of insulin therapy to prevent acute complications
  • New Onset Diabetes after Transplant (NODAT)
    • Incidence is not known due to varying study methodology
    • Risk factors
      • Patient factors: Older age, obesity, African American race, hispanic ethnicity, family hx of DM, hx of gestational DM
      • Transplant factors: Meds (steroids, calcineurin inhibitors, mTOR inhibitors)
      • Other: HCV, preoperative hyperglycemia, hypomagnesemia
    • All patients should have post-op glucose checks weekly for first four weeks, then at 3 and 6 months and then yearly. A1c should be checked 3 months post-op

Evernote link to Ambulatory Report Pearls:

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!