Summary

Iodine nutrition is a growing issue within the USA due to newer trends of non-iodized salts. There are no recent reviews looking at the current state of iodine deficiency-induced hypothyroidism in children in the USA. We performed a retrospective chart review at our tertiary pediatric endocrine clinic; four met the diagnostic criteria for iodine deficiency defined by a low urine iodine level. We further characterized severity of disease, risk factors, goiter, thyroid labs and antibodies. All cases had significant goiter and were diagnosed within the last 2 years. One case had iodine deficiency due to no iodized salt intake along with concurrent diagnosis of developmental delay and multiple food allergies, while others involved the use of non-iodized salts. Two cases had iodine deficiency along with autoimmunity. It is critical to obtain a dietary history for all patients who present with goiter and/or hypothyroidism. There may be a need to consider reevaluating current preventative measures for iodine deficiency, especially for certain vulnerable populations such as children who do not consume iodized salt.

Learning points

• In recent decades, iodine nutrition has become a growing concern due to changing dietary patterns and food manufacturing practices.

• A dietary history is crucial to obtain in children presenting with hypothyroidism and goiter, especially in children with restrictive diets due to behavioral concerns, developmental delays, or multiple food allergies.

• Of the 12 different types of salts commercially available, only table salt contains iodine in an appropriate amount; thus, individuals using specialty salts can develop mild to moderate iodine deficiency-related thyroid disease.

Summary

A previously healthy 17-year-old female presented to the emergency department with complaints of vomiting, shortness of breath, and tachycardia. She was found to have an elevated blood glucose and was admitted for presumed new onset type 1 diabetes mellitus (T1DM). During the admission, she was noted to have frequent episodes of hypoglycemia despite conservative insulin dosing and high urine output with glucosuria, which seemed out of proportion to her glucose levels and fluid status. She also had persistent hyponatremia despite normalization of blood glucose. Further work-up was initiated to investigate alternative or additional diagnoses to explain these atypical findings. Adrenocorticotropic hormone (ACTH) level was elevated, consistent with the diagnosis of Addison’s disease, which led to the subsequent diagnosis of autoimmune polyglandular syndrome type II (APS-2). This is one of the first reports in the literature of concurrent diagnosis of T1DM and Addison’s disease at initial presentation and demonstrates the importance of not anchoring to one diagnosis.

Learning points

• This case shows the importance of considering multiple diagnoses and investigating atypical signs and symptoms.

• This case highlights the importance of a thorough history including review of systems.

• Hyponatremia and recurrent hypoglycemia in a person with type 1 diabetes should raise suspicion for adrenal insufficiency.

• This case makes us consider the screening for Addison’s disease in a person with new onset type 1 diabetes in addition to autoimmune thyroid disease and celiac disease.

• People with an autoimmune disease should be monitored for other autoimmune diseases in the future.

Summary

Thyroid cancer is one of the most common manifestations of Cowden syndrome, yet the syndrome is rare. The incidence of Cowden syndrome is 1 in 200,000. The diagnosis can be made clinically when patients present with a combination of symptoms such as mucocutaneous lesions with a strong personal or family history of thyroid, breast, endometrial, and colorectal cancer. A high index of suspicion is required to provide a clinical diagnosis utilizing major and minor criteria. Once a clinical diagnosis is made, genetic testing for a PTEN mutation, a tumor suppressor gene, is recommended. Cancer surveillance should be performed for those with positive genetic testing as well as those with negative genetic testing who still meet clinical diagnostic criteria. We present two cases of Cowden syndrome: one case involving an increasing number of thyroid nodules in a patient with known Cowden syndrome and another patient with a strong family history of cancer, personal history of follicular thyroid cancer, and numerous colonic polyps on screening colonoscopy. These cases demonstrate how early diagnosis of Cowden syndrome can help detect early cancer in both the patient and affected relatives.

Learning points

• Diagnosing Cowden syndrome helps pre-risk stratification for early cancer screening.

• The diagnosis of Cowden syndrome can be made with a combination of major and minor criteria: any two major criteria with or without a minor criterion; one major and one minor criterion; or three minor criteria.

• Patients who meet the diagnostic criteria for Cowden syndrome should undergo genetic screening.

Summary

Kallmann syndrome (KS) is a genetically heterogeneous condition characterized by hypogonadotropic hypogonadism with coexisting anosmia or hyposmia along with potential other phenotypic abnormalities depending on the specific genetic mutation involved. Several genetic mutations have been described to cause KS. The ANOS1 (KAL1) gene is responsible for 8% of mutations causing KS. A 17-year-old male presented to our clinic with delayed puberty and hyposmia, along with a family history suggestive of hypogonadism in his maternal uncle. Genetic testing for KS revealed complete exon 3 deletion in the ANOS1 gene. To the best of our knowledge, this specific mutation has not been previously described in the literature.

Learning points

• Missense and frameshift mutations in the KAL1 or ANOS1 gene located in the X chromosome are responsible for 8% of all known genetic mutations of Kallmann syndrome.

• Exon 3 deletion is one of the ANOS1 gene is a novel mutation, not reported before.

• Targeted gene sequencing for hypogonadotropic hypogonadism can be employed based on the phenotypic presentation.

Summary

Multiple research studies address the anti-insulinemic effect of growth hormone (GH). We report a case of a patient with anterior hypopituitarism on GH replacement who later developed type 1 diabetes mellitus (T1DM). Recombinant human growth hormone (rhGH) therapy was discontinued at the time of growth completion. Because of significantly improved glycemic control, this patient was weaned off subcutaneous insulin. He regressed from stage 3 to stage 2 T1DM and remained in this status for at least 2 years and until the writing of this paper. The diagnosis of T1DM was established based on relatively low C-peptide and insulin levels for the degree of hyperglycemia as well as seropositivity of zinc transporter antibody and islet antigen-2 antibody. Additional laboratory data obtained 2 months after discontinuing rhGH revealed improved endogenous insulin secretion. This case report calls attention to the diabetogenic effect of GH therapy in the setting of T1DM. It also demonstrates the possibility of regression from stage 3 T1DM requiring insulin therapy to stage 2 T1DM with asymptomatic dysglycemia after discontinuing rhGH.

Learning points

• Given the diabetogenic effect of growth hormone, blood glucose levels should be monitored in patients with type 1 diabetes mellitus (T1DM) on insulin therapy and recombinant human growth hormone (rhGH) replacement.

• Clinicians should closely monitor for risk of hypoglycemia after discontinuing rhGH among T1DM patients who are on insulin treatment.

• The discontinuation of rhGH in the setting of T1DM may cause regression of symptomatic T1DM to asymptomatic dysglycemia requiring no insulin treatment.

Summary

We describe a case of a 47-year-old patient who presented with severe lactic acidosis, troponinemia, and acute kidney injury after receiving 8 mg of intramuscular dexamethasone for seasonal allergies in the setting of an undiagnosed epinephrine-secreting pheochromocytoma. This case was atypical, however, in that the patient exhibited only mildly elevated noninvasive measured blood pressures. Following a period of alpha-adrenergic blockade, the tumor was resected successfully. Steroid administration can precipitate pheochromocytoma crisis that may present unusually as in our patient with mild hypertension but profound lactic acidosis.

Learning points

• Steroids administered via any route can precipitate pheochromocytoma crisis, manifested by excessive catecholamine secretion and associated sequelae from vasoconstriction.

• Lack of moderate/severe hypertension on presentation detracts from consideration of pheochromocytoma as a diagnosis.

• Lactatemia after steroid administration should prompt work-up for pheochromocytoma, as it can be seen in epinephrine-secreting tumors.

• Noninvasive blood pressure measurements may be unreliable during pheochromocytoma crisis due to excessive peripheral vasoconstriction.

Summary

Anaphylaxis is a rapidly progressive potentially lethal condition, and epinephrine is the most crucial medication in its treatment. In this study, we present a case of diabetic ketoacidosis in a young woman that was precipitated by the administration of epinephrine to treat anaphylaxis. This patient had diabetes mellitus and poor glycemic control and developed ketoacidosis despite having evidence of ongoing endogenous insulin production and having been treated with exogenous long-acting insulin less than 24 h prior to the event. This is a rare, serious, adverse side effect of life-saving medication. This report demonstrates that the risk of diabetic ketoacidosis should be considered when administering epinephrine to patients with diabetes, even in the absence of complete insulin deficiency.

Learning points

• Epinephrine directly suppresses insulin secretion, stimulates lipolysis, and causes ketone body generation.

• High-dose catecholamine administration can cause unexpected diabetic ketoacidosis in patients with risk factors.

• Early administration of insulin may not protect patients from developing ketoacidosis in the setting of high-dose catecholamine administration.

Summary

Increased intracranial pressure (ICP) can present with symptoms of headache, vomiting, visual changes, and tinnitus. Papilledema may be seen on physical exam. Thyroid disease has been a rare secondary cause of increased ICP. We present a 16-year-old female who had a worsening headache for 6 months. She was found to have signs, symptoms, physical exam findings, and diagnostic studies consistent with both increased ICP and previously undiagnosed Graves’ disease. The patient was treated with a 19-month course of methimazole 40 mg daily. Her headache and papilledema resolved shortly after medication initiation. The timeline of symptoms and resolution of her increased ICP symptoms with treatment of Graves’ disease suggests that hyperthyroidism was the underlying cause of her increased ICP. Clinicians should consider Graves’ disease as the etiology in pediatric patients presenting with signs and symptoms of increased ICP with papilledema.

Learning points

• Symptoms of increased intracranial pressure (ICP) include headache, vomiting, transient visual changes, and tinnitus.

• Secondary causes of increased ICP should be considered in males, young children, older patients, and those not overweight.

• Clinicians should consider Graves’ disease as the etiology in pediatric patients presenting with signs and symptoms of increased ICP with papilledema. They should assess for orbitopathy and thyromegaly and inquire about symptoms that would be indicative of hyperthyroidism.

Summary

We identified an adolescent young woman with new-onset diabetes. Due to suspicious family history, she underwent genetic testing for common monogenic diabetes (MODY) genes. We discovered that she and her father carry a novel variant of uncertain significance in the HNF1A gene. She was successfully transitioned from insulin to a sulfonylurea with excellent glycemic control. Based on her family history and successful response to sulfonylurea, we propose that this is a novel pathogenic variant in HNF1A. This case highlights the utility of genetic testing for MODY, which has the potential to help affected patients control their diabetes without insulin.

Learning points

• HNF1A mutations are a common cause of monogenic diabetes in patients presenting with early-onset diabetes and significant family history.

• Genetic testing in suspected patients allows for the identification of mutations causing monogenic diabetes.

• First-degree relatives of the affected individual should be considered for genetic testing.

• The use of sulfonylurea agents in patients with HNF1A-MODY can reduce dependence on insulin therapy and provide successful glycemic control.

Summary

Insulinomas are a rare cause of persistent hypoglycemia in a previously healthy child. In addition to symptoms of hypoglycemia, individuals with insulinomas usually present with a history of incessant caloric intake and weight gain due to a constant need to counter hypoglycemia. In addition to an extensive review of the literature, we report the first case of an insulinoma coexisting with reduced appetite secondary to anorexia nervosa in an adolescent female.

Learning points

• Eliciting a detailed family history is important in hypoglycemia cases.

• Obtaining a thorough dietary intake, weight history, and menstrual cycles (in females) and considering a psychiatric consultation for an eating disorder when indicated.

• Although rare in the pediatric population, multiple endocrine neoplasia type 1 syndrome should be considered in the evaluation of children and adolescents with hypoglycemia who also have a family history of pituitary, pancreatic, and/or parathyroid endocrinopathies.