Search for other papers by M Horsey in
Google Scholar
PubMed
Search for other papers by P Hogan in
Google Scholar
PubMed
Search for other papers by T Oliver in
Google Scholar
PubMed
Summary
A 71-year-old woman with severe right lower leg pain, edema and erythema was presented to the Emergency Department and was found to have an extensive deep vein thrombosis (DVT) confirmed by ultrasound. She underwent an extensive evaluation due to her prior history of malignancy and new hypercoagulable state, but no evidence of recurrent disease was detected. Further investigation revealed pernicious anemia (PA), confirmed by the presence of a macrocytic anemia (MCV=115.8fL/red cell, Hgb=9.0g/dL), decreased serum B12 levels (56pg/mL), with resultant increased methylmalonic acid (5303nmol/L) and hyperhomocysteinemia (131μmol/L), the presumed etiology of the DVT. The patient also suffered from autoimmune thyroid disease (AITD), and both antithyroglobulin and anti-intrinsic factor antibodies were detected. She responded briskly to anticoagulation with heparin and coumadin and treatment of PA with intramuscular vitamin B12 injections. Our case suggests that a DVT secondary to hyperhomocystenemia may represent the first sign of polyglandular autoimmune syndrome III-B (PAS III-B), defined as the coexistent autoimmune conditions AITD and PA. It is important to recognize this clinical entity, as patients may not only require acute treatment with vitamin B12 supplementation and prolonged anticoagulation, as in this patient, but may also harbor other autoimmune diseases.
Learning points
-
A DVT can be the first physical manifestation of a polyglandular autoimmune syndrome.
-
Hyperhomocysteinemia secondary to pernicious anemia should be considered as an etiology of an unprovoked DVT in a euthyroid patient with autoimmune thyroid disease.
-
Patients with DVT secondary to hyperhomocysteinemia should undergo screening for the presence of co-existent autoimmune diseases in addition to treatment with B12 supplementation and anticoagulation to prevent recurrent thromboembolism.
Department of Medicine, Waterbury Hospital, Waterbury, Connecticut, USA
Search for other papers by S M Kandel in
Google Scholar
PubMed
Department of Medicine, Waterbury Hospital, Waterbury, Connecticut, USA
Search for other papers by J A Cosgriff in
Google Scholar
PubMed
Summary
Clinicians are often presented with the scenario of what to do when one medication in a drug class has failed a therapeutic trial on a patient. We encountered a patient who developed profound resistance to glargine, aspart and regular insulin, but had a rapid and sustained response to detemir. The mechanism of the increased sensitivity to detemir is unclear, but may be related to an additional carbon chain on detemir shielding it from an antibody response. This case highlights the profound impact that subtle differences in molecular structure can have on biological activity and thus patient outcomes.
Learning points
-
Subtle differences in molecular structure can have a profound impact on biological activity, and thus patient outcomes.
-
Poor outcomes with one medication in a drug class should not be used to rule out the efficacy of all related medications.
-
Detemir has been shown to be less immunogenic than other insulins, and should be considered in patients with insulin resistance.
Search for other papers by Jasmeet Kaur in
Google Scholar
PubMed
Search for other papers by Luis Casas in
Google Scholar
PubMed
Anderson Cancer Institute, Memorial University Medical Center, Savannah, Georgia, 31404, USA
Search for other papers by Himangshu S Bose in
Google Scholar
PubMed
Summary
Lipoid congenital adrenal hyperplasia (lipoid CAH), the most severe form of CAH, is most commonly caused by mutations in steroidogenic acute regulatory protein (STAR), which is required for the movement of cholesterol from the outer to the inner mitochondrial membranes to synthesize pregnenolone. This study was performed to evaluate whether the salt-losing crisis and the adrenal inactivity experienced by a Scandinavian infant is due to a de novo STAR mutation. The study was conducted at the University of North Dakota, the Mercer University School of Medicine and the Memorial University Medical Center to identify the cause of this disease. The patient was admitted to a pediatric endocrinologist at the Sanford Health Center for salt-losing crisis and possible adrenal failure. Lipoid CAH is an autosomal recessive disease, we identified two de novo heterozygous mutations (STAR c.444C>A (STAR p.N148K) and STAR c.557C>T (STAR p.R193X)) in the STAR gene, causing lipoid CAH. New onset lipoid CAH can occur through de novo mutations and is not restricted to any specific region of the world. This Scandinavian family was of Norwegian descent and had lipoid CAH due to a mutation in S TAR exons 4 and 5. Overexpression of the STAR p.N148K mutant in nonsteroidogenic COS-1 cells supplemented with an electron transport system showed activity similar to the background level, which was ∼10% of that observed with wild-type (WT) STAR. Protein-folding analysis showed that the finger printing of the STAR p.N148K mutant is also different from the WT protein. Inherited STAR mutations may be more prevalent in some geographical areas but not necessarily restricted to those regions.
Learning points
-
STAR mutations cause lipoid CAH.
-
This is a pure population from a caucasian family.
-
Mutation ablated STAR activity.
-
The mutation resulted in loosely folded conformation of STAR.
Search for other papers by Yael R Nobel in
Google Scholar
PubMed
Search for other papers by Maya B Lodish in
Google Scholar
PubMed
Search for other papers by Margarita Raygada in
Google Scholar
PubMed
Search for other papers by Jaydira Del Rivero in
Google Scholar
PubMed
Search for other papers by Fabio R Faucz in
Google Scholar
PubMed
Search for other papers by Smita B Abraham in
Google Scholar
PubMed
Search for other papers by Charalampos Lyssikatos in
Google Scholar
PubMed
Search for other papers by Elena Belyavskaya in
Google Scholar
PubMed
Search for other papers by Constantine A Stratakis in
Google Scholar
PubMed
Johns Hopkins University School of Medicine, Division of Endocrinology, Diabetes, and Metabolism, Baltimore, Maryland, 21287, USA
Suburban Hospital, Bethesda, Maryland, 20814, USA
Search for other papers by Mihail Zilbermint in
Google Scholar
PubMed
Summary
Autosomal recessive pseudohypoaldosteronism type 1 (PHA1) is a rare disorder characterized by sodium wasting, failure to thrive, hyperkalemia, hypovolemia and metabolic acidosis. It is due to mutations in the amiloride-sensitive epithelial sodium channel (ENaC) and is characterized by diminished response to aldosterone. Patients may present with life-threatening hyperkalemia, which must be recognized and appropriately treated. A 32-year-old female was referred to the National Institutes of Health (NIH) for evaluation of hyperkalemia and muscle pain. Her condition started in the second week of life, when she was brought to an outside hospital lethargic and unresponsive. At that time, she was hypovolemic, hyperkalemic and acidotic, and was eventually treated with sodium bicarbonate and potassium chelation. At the time of the presentation to the NIH, her laboratory evaluation revealed serum potassium 5.1 mmol/l (reference range: 3.4–5.1 mmol/l), aldosterone 2800 ng/dl (reference range: ≤21 ng/dl) and plasma renin activity 90 ng/ml/h (reference range: 0.6–4.3 ng/ml per h). Diagnosis of PHA1 was suspected. Sequencing of the SCNN1B gene, which codes for ENaC, revealed that the patient is a compound heterozygote for two novel variants (c.1288delC and c.1466+1 G>A), confirming the suspected diagnosis of PHA1. In conclusion, we report a patient with novel variants of the SCNN1B gene causing PHA1 with persistent, symptomatic hyperkalemia.
Learning points
-
PHA1 is a rare genetic condition, causing functional abnormalities of the amiloride-sensitive ENaC.
-
PHA1 was caused by previously unreported SCNN1B gene mutations (c.1288delC and c.1466+1 G>A).
-
Early recognition of this condition and adherence to symptomatic therapy is important, as the electrolyte abnormalities found may lead to severe dehydration, cardiac arrhythmias and even death.
-
High doses of sodium polystyrene sulfonate, sodium chloride and sodium bicarbonate are required for symptomatic treatment.
Search for other papers by Maura Bucciarelli in
Google Scholar
PubMed
Search for other papers by Ya-Yu Lee in
Google Scholar
PubMed
Search for other papers by Vasudev Magaji in
Google Scholar
PubMed
Summary
Ectopic ACTH secretion from breast cancer is extremely rare. We report a case of a 30-year-old woman with a history of breast cancer, who presented with psychosis and paranoid behaviour. CT of the head showed white matter disease consistent with posterior reversible encephalopathy syndrome (PRES). Despite using mifepristone with multiple antihypertensives including lisinopril, spironolactone and metoprolol, she was hypertensive. Transaminitis did not allow mifepristone dose escalation and ketoconazole utilization. Etomidate infusion at a non-sedating dose in the intensive care unit controlled her hypertension and cortisol levels. She was transitioned to metyrapone and spironolactone. She was discharged from the hospital on metyrapone with spironolactone and underwent chemotherapy. She died 9 months later after she rapidly redeveloped Cushing's syndrome and had progressive metastatic breast cancer involving multiple bones, liver and lungs causing respiratory failure.
Learning points
-
Cushing's syndrome from ectopic ACTH secreting breast cancer is extremely rare.
-
Cushing's syndrome causing psychosis could be multifactorial including hypercortisolism and PRES.
-
Etomidate at non-sedating doses in intensive care setting can be effective to reduce cortisol production followed by transition to oral metyrapone.
Search for other papers by Geetanjali Kale in
Google Scholar
PubMed
Search for other papers by Elaine M Pelley in
Google Scholar
PubMed
Search for other papers by Dawn Belt Davis in
Google Scholar
PubMed
Summary
Myelolipomas have been reported in patients with congenital adrenal hyperplasia (CAH). ACTH excess, as seen with non-adherence to glucocorticoid therapy, may be responsible for tumor development. We report a case of a 51-year-old man with classic salt-wasting CAH managed on prednisone 7.5 mg daily and fludrocortisone who presented with chronic back pain and was found to have giant bilateral retroperitoneal masses. On computed tomography (CT) imaging, the masses were heterogeneous, but contained predominantly low-density fat attenuation. The tumors were resected due to concern for malignancy and mass symptoms. Pathologic examination identified both retroperitoneal masses as myelolipomas. The left tumor was 34×20×13 cm and weighed 4.7 kg and the right tumor was 20 cm in the largest dimension. Adrenal tissue was present in the specimen. The patient reported long-term compliance with glucocorticoid treatment. However, no biochemical monitoring of ACTH levels had occurred. Therefore, it is unclear if ACTH excess contributed to the development of these large tumors in this patient. It was presumed that both adrenal glands were inadvertently removed during surgery and the patient was treated with physiologic replacement doses of hydrocortisone and fludrocortisone postoperatively. In this case, the bilateral adrenalectomy was inadvertent. However, adrenalectomy can be considered as a treatment option in patients with classical CAH under certain circumstances to avoid complications of glucocorticoid excess.
Learning points
-
Myelolipomas should be considered in the differential diagnosis of adrenal or retroperitoneal masses in patients with CAH.
-
On CT imaging, myelolipomas are seen as heterogeneous masses with low-density mature fat interspersed with more dense myeloid tissue.
-
Myelolipomas are usually unilateral and measure <4 cm; however, very large and bilateral tumors have been reported.
-
Treatment of CAH typically involves using supraphysiologic doses of glucocorticoid to suppress adrenal hyperandrogenism. Bilateral adrenalectomy is an alternative treatment option in patients with CAH.
-
There is an association between ACTH excess and increased incidence of adrenal myelolipoma but the direct causal link remains to be established.
Search for other papers by Arshpreet Kaur in
Google Scholar
PubMed
Search for other papers by Stephen J Winters in
Google Scholar
PubMed
Summary
Drugs that inhibit the sodium-glucose co-transporter-2 (SGLT2) are an exciting novel, insulin-independent treatment for diabetes that block glucose reabsorption from the proximal tubules of the kidney, leading to increased glucose excretion and lower blood glucose levels. Inhibition of SGLT2 activity also reduces sodium reabsorption, which together with glycosuria produces a mild diuretic effect with the potential for dehydration and hyperkalemia. We report on a 60-year-old man with uncontrolled type 2 diabetes treated with insulin, glimepiride, metformin and canagliflozin, who was admitted with altered mental status after a syncopal episode. He had a 1-week history of ingestion of Tums for heartburn followed by poor appetite and lethargy. Laboratory work-up showed acute kidney injury, diabetic ketoacidosis (DKA), and parathyroid hormone-independent severe hypercalcemia of 17.4 mg/dl. DKA resolved with insulin treatment, and saline hydration led to improvement in hypercalcemia and renal function over 48 h, but was accompanied by a rapid increase in the serum sodium concentration from 129 to 162 mmol/l despite changing fluids to 0.45% saline. Urine studies were consistent with osmotic diuresis. Hypernatremia was slowly corrected with hypotonic fluids, with improvement in his mental status over the next 2 days. This is the first report of hypercalcemia associated with the use of a SLGT2 inhibitor. Although the exact mechanism is unknown, canagliflozin may predispose to hypercalcemia in patients ingesting excessive calcium because of dehydration from osmotic diuresis, with reduced calcium excretion and possible increased intestinal calcium absorption. Saline therapy and osmotic diuresis may lead to hypernatremia from electrolyte-free water loss.
Learning points
-
Canagliflozin, an SGLT2 inhibitor, may cause hypercalcemia in susceptible patients.
-
Although the exact mechanisms are unknown, dehydration from osmotic diuresis and increased intestinal calcium absorption play a role.
-
Close monitoring of serum calcium levels is recommended in patients treated with SGLT2 inhibitors who are elderly, have established hypercalcemia, or take oral calcium supplements.
-
Saline therapy and osmotic diuresis may lead to hypernatremia from electrolyte-free water loss in susceptible patients.
Search for other papers by Marisa M Fisher in
Google Scholar
PubMed
Search for other papers by Susanne M Cabrera in
Google Scholar
PubMed
Division of Endocrinology, Department of Medicine, Indiana University School of Medicine, 541 North Clinical Drive, Indianapolis, Indiana, 46202, USA
Search for other papers by Erik A Imel in
Google Scholar
PubMed
Summary
Neonatal severe hyperparathyroidism (NSHPT) is a rare disorder caused by inactivating calcium-sensing receptor (CASR) mutations that result in life-threatening hypercalcemia and metabolic bone disease. Until recently, therapy has been surgical parathyroidectomy. Three previous case reports have shown successful medical management of NSHPT with cinacalcet. Here we present the detailed description of two unrelated patients with NSHPT due to heterozygous R185Q CASR mutations. Patient 1 was diagnosed at 11 months of age and had developmental delays, dysphagia, bell-shaped chest, and periosteal bone reactions. Patient 2 was diagnosed at 1 month of age and had failure to thrive, osteopenia, and multiple rib fractures. Cinacalcet was initiated at 13 months of age in patient 1, and at 4 months of age in patient 2. We have successfully normalized their parathyroid hormone and alkaline phosphatase levels. Despite the continuance of mild hypercalcemia (11–12 mg/dl), both patients showed no hypercalcemic symptoms. Importantly, patient 1 had improved neurodevelopment and patient 2 never experienced any developmental delays after starting cinacalcet. Neither experienced fractures after starting cinacalcet. Both have been successfully managed long-term without any significant adverse events. These cases expand the current literature of cinacalcet use in NSHPT to five successful reported cases. We propose that cinacalcet may be considered as an option for treating the severe hypercalcemia and metabolic bone disease found in infants and children with inactivating CASR disorders.
Learning points
-
NSHPT due to mutations in the CASR gene occurs with hypercalcemia and metabolic bone disease, but not always with severe critical illness in infancy.
-
NSHPT should be considered in the differential diagnosis for a newborn with a bell-shaped chest, osteopenia, and periosteal reactions.
-
Neurodevelopmental consequences may occur in children with hypercalcemia and may improve during treatment.
-
Calcimimetics can be used to successfully treat the pathophysiology of NSHPT directly to control serum calcium levels.
Search for other papers by Mohammed Al-Sofiani in
Google Scholar
PubMed
Search for other papers by Dhimitri Nikolla in
Google Scholar
PubMed
Search for other papers by V V S Ramesh Metta in
Google Scholar
PubMed
Summary
We report the case of a 42-year-old female with a history of hypothyroidism and asthma presenting with progressive dyspnea and orthopnea after 2 days of an upper respiratory tract infection (URTI). Based on the clinical and radiological findings, the patient was admitted as a case of cardiogenic pulmonary edema secondary to possible viral myocarditis. However, a normal brain natriuretic peptide (BNP) level with a normal ejection fraction (EF) on echocardiogram changed our working diagnosis from cardiogenic to non-cardiogenic pulmonary edema. Further questioning revealed a history of nocturnal snoring, frequent awakening, and daytime fatigue, suggesting a possible sleep apnea syndrome (SAS). In conclusion, we believe that SAS was the missing link between our patient's hypothyroidism and non-cardiogenic pulmonary edema.
Learning points
-
Always keep an open mind and look for a pathology that would explain the whole clinical scenario.
-
The involvement of the respiratory system in hypothyroidism can range from SAS, pulmonary hypertension, hypoventilation, and severe respiratory failure.
-
Hypothyroidism and SAS should be considered in the differential diagnosis of non-cardiogenic pulmonary edema.
-
Patients should be instructed to take levothyroxine on an empty stomach 30–60 min before food to avoid erratic absorption of the hormone.
Search for other papers by Naweed Alzaman in
Google Scholar
PubMed
Search for other papers by Anastassios G Pittas in
Google Scholar
PubMed
Search for other papers by Miriam O'Leary in
Google Scholar
PubMed
Search for other papers by Lisa Ceglia in
Google Scholar
PubMed
Summary
Transient hypocalcemia after thyroidectomy is not uncommon and the risk increases with the extent of neck surgery. We report a case of severe and prolonged hypocalcemia after total thyroidectomy complicated by thoracic duct injury. Hypoparathyroidism and thoracic duct injury are potential complications following total thyroidectomy with extensive lymph node dissection. This case suggested that having both conditions may complicate treatment of hypoparathyroid-induced hypocalcemia by way of losses of calcium and vitamin D in the chyle leak.
Learning points
-
This report highlights chyle leak as an uncommon cause of prolonged hypocalcemia in patients who have undergone extensive neck surgery.
-
Chyle has an electrolyte concentration similar to that of plasma.
-
Medical treatment options for a chyle leak include fat-free oral diet or parenteral nutrition without oral intake, pharmacological treatment (primarily octreotide).
