Self-Reported Allergy to Thyroid Replacement Therapy: A Multicenter Retrospective Chart Review.

OBJECTIVE: To determine patterns of adverse drug reactions (ADRs), including immediate drug hypersensitivity reactions (DHRs) and predictable ADRs, to thyroid replacement therapy (TRT). TRT is the treatment of choice for hypothyroidism. Levothyroxine (LT4) is among the most commonly prescribed medications in the United States, with over 70 million prescriptions annually. Documented immediate DHRs to TRT are rare, with only a few case reports. METHODS: An 11-year (2008-2018) retrospective medical chart review of identified patients with self-reported allergy to TRT. ADRs to TRT were divided into immediate DHRs and predictable ADRs. RESULTS: A total of 466 patients were included in our study. We found an overall incidence of ADRs to TRT of 0.3%. Median age was 61.2 years; 85.8% were women, and 94.4% were Caucasian. The principal indication for TRT was autoimmune hypothyroidism (73.6%), followed by postsurgical hypothyroidism (17.4%) and subclinical hypothyroidism (6.7%). Predictable ADR manifestations to TRT were reported more commonly than DHR manifestations (57.5% vs. 42.5%, respectively). The most frequently reported of the former were palpitations (16.4%), nausea/vomiting (9.3%), and tremor (6.3%), while rash (23.8%), hives (9.5%), and pruritus (7.1%) were the most common regarding the latter. Fifty-six percent of the patients with an ADR to TRT tolerated an alternative TRT presentation. CONCLUSION: In our cohort, the majority of self-reported allergies to TRT were due to predictable ADRs rather than an immediate DHR. ABBREVIATIONS: ADR = adverse drug reaction; DHR = drug hypersensitivity reaction; FDA = Food and Drug Administration; LT3 = liothyronine; LT4 = levothyroxine; SCAR = severe cutaneous adverse drug reaction; TRT = thyroid replacement therapy.

The clinical presentation of PIT1 positive pituitary neuroendocrine tumor immunonegative for growth hormone, prolactin, and thyroid stimulating hormone with analysis of clinical and immunostaining dissociation.

BACKGROUND: PIT1 is a pituitary transcription factor that is associated with either growth hormone (GH), prolactin (PRL), or thyroid-stimulating hormone (TSH) production. However, PIT1-positive pituitary neuroendocrine tumors (PitNETs) are occasionally immunonegative for GH, PRL, and TSH. This paper describes the clinical presentation of PIT1 positive however immunonegative PitNETs. METHODS: We conducted a retrospective analysis, identifying 228 PIT1-positive PitNET patients between 2017 and 2022. Out of these, ten (4%) tested negative for GH, PRL, and TSH. Functioning PitNETs were defined as those causing hormonal excess symptoms or hormonal overproduction. RESULTS: As for 10 patients immunonegative for all three hormones however PIT1-positive, the mean ( ± standard deviation) age was 46 ± 13 years with 70% women. Six patients exhibited signs of excess GH or PRL, and three had visual problems. Additionally, one patient had secondary hypothyroidism and adrenal insufficiency resulting from the mass effect. All tumors were macroadenoma, with a median volume of 2.1 cm3 (range, 0.8-17.5 cm3). Gross total resection was attained in six patients by trans-sphenoidal surgery. Postoperatively, eight patients experienced clinical improvement: three in vision, two in amenorrhea, two in headache, and one in acromegaly symptoms. Biochemical improvement was observed in six patients, with all experiencing remission in hormonal excess and one showing improvement in secondary hypothyroidism. Stereotactic radiosurgery was performed in three patients. CONCLUSIONS: Patients with functioning PitNETs may exhibit PIT1 staining without GH, PRL, or TSH staining. Hormonally active tumors exist in this patient population; therefore, close endocrine follow-up is necessary despite the lack of staining for GH, PRL, and TSH.

Diagnosis of a pheochromocytoma.

Although rare, pheochromocytomas are potentially lethal tumors. Thus, it is important that physicians be able to diagnose these tumors. The definitive diagnosis of a pheochromocytoma rests on demonstrating catecholamine overproduction. Once the diagnosis is established, computed tomography scan, magnetic resonance imaging, and metaiodobenzylguanidine studies are utilized for localizing the tumor. This paper reviews the biochemical and radiologic studies useful for evaluating a patient for the possibility of a pheochromocytoma.

Clinical and molecular features of Hürthle cell carcinoma of the thyroid.

CONTEXT: Hürthle cell cancer (HCC) of the thyroid remains the subject of controversy with respect to natural course, treatment, and follow-up. OBJECTIVE: The objective of the study was to evaluate the clinical and molecular features associated with outcome in HCC. DESIGN: The study was a review of 173 HCC cases treated at Mayo Clinic over 11 years with a median 5.8-year follow-up. RESULTS: None of the patients with minimally invasive histology had persistent disease, clinical recurrence, or disease-related death. Male gender and TNM stage were independently associated with increased risk of clinical recurrence or death in widely invasive patients. The 5-year cumulative probability of clinical recurrence or death was higher in patients with TNM stage III-IV (females, 74%; males, 91%) compared with patients with TNM stage I-II (females, 0%; males, 17%). Pulmonary metastases were best identified by computed tomography, whereas radioactive iodine scans were positive in only two of 27 cases. Thyroglobulin was detectable in patients with clinical disease, with the notable exception of five patients with distant metastases. The common TERT C228T promoter mutation was detected in both widely invasive and minimally invasive tumors. TERT mRNA was below the limit of detection in all samples. CONCLUSION: Widely invasive HCC with TNM stage III-IV is aggressive, with low probability of recurrence-free survival. Males have worse outcomes than females. Minimally invasive HCC appears to be considerably less aggressive. Radioactive iodine scan performs poorly in detecting distant disease. Although the TERT gene is mutated in HCC, the role of this mutation remains to be demonstrated.

Nicotine-substitute gum-induced milk alkali syndrome: a look at unexpected sources of calcium.

OBJECTIVE: This report describes a 64-year-old woman with recurrent hypercalcemia. Her laboratory evaluation was consistent with milk-alkali syndrome. It was eventually discovered that the source of the excessive calcium consumption was nicotine-replacement chewing gum and carbonated water. METHODS: An extensive literature search was performed to see if milk-alkali syndrome due to nicotine-replacement gum and carbonated water has been previously reported. RESULTS: No prior report describing the association of milk alkali syndrome with nicotine-replacement gum and carbonated water was found. CONCLUSION: We present a unique case of milk-alkali syndrome due to nicotine-replacement gum and carbonated water. It serves as a lesson to evaluate other sources besides calcium supplements as the cause of excessive calcium intake.

Development of a multidisciplinary, multicampus subspecialty practice in endocrine cancers.

OBJECTIVES: Relative to more abundant neoplasms, endocrine cancers have been historically neglected, yet their incidence is increasing. We therefore sought to build interest in endocrine cancers, improve physician experience, and develop innovative approaches to treating patients with these neoplasms. METHODS: Between 2005 and 2010, we developed a multidisciplinary Endocrine Malignancies Disease Oriented Group involving all 3 Mayo Clinic campuses (Rochester, Minnesota; Jacksonville, Florida; and Scottsdale, Arizona). In response to higher demand at the Rochester campus, we sought to develop a Subspecialty Tumor Group and an Endocrine Malignancies Tumor Clinic within the Division of Medical Oncology. RESULTS: The intended groups were successfully formed. We experienced difficulty in integration of the Mayo Scottsdale campus resulting from local uncertainty as to whether patient volumes would be sufficient to sustain the effort at that campus and difficulty in developing enthusiasm among clinicians otherwise engaged in a busy clinical practice. But these obstacles were ultimately overcome. In addition, with respect to the newly formed medical oncology subspecialty endocrine malignancies group, appointment volumes quadrupled within the first year and increased 7 times within 2 years. The number of active therapeutic endocrine malignancies clinical trials also increased from 1 in 2005 to 5 in 2009, with all 3 Mayo campuses participating. CONCLUSIONS: The development of subspecialty tumor groups for uncommon malignancies represents an effective approach to building experience, increasing patient volumes and referrals, and fostering development of increased therapeutic options and clinical trials for patients afflicted with otherwise historically neglected cancers.

Development of a multidisciplinary, multicampus subspecialty practice in endocrine cancers.

PURPOSE: Relative to more abundant neoplasms, endocrine cancers have been historically neglected, yet their incidence is increasing. We therefore sought to build interest in endocrine cancers, improve physician experience, and develop innovative approaches to treating patients with these neoplasms. METHODS: Between 2005 and 2010, we developed a multidisciplinary Endocrine Malignancies Disease Oriented Group involving all three Mayo Clinic campuses (Rochester, MN; Jacksonville, FL; and Scottsdale, AZ). In response to higher demand at the Rochester campus, we sought to develop a Subspecialty Tumor Group and an Endocrine Malignancies Tumor Clinic within the Division of Medical Oncology. RESULTS: The intended groups were successfully formed. We experienced difficulty in integration of the Mayo Scottsdale campus resulting from local uncertainty as to whether patient volumes would be sufficient to sustain the effort at that campus and difficulty in developing enthusiasm among clinicians otherwise engaged in a busy clinical practice. But these obstacles were ultimately overcome. In addition, with respect to the newly formed medical oncology subspecialty endocrine malignancies group, appointment volumes quadrupled within the first year and increased seven times within two years. The number of active therapeutic endocrine malignancies clinical trials also increased from one in 2005 to five in 2009, with all three Mayo campuses participating. CONCLUSION: The development of subspecialty tumor groups for uncommon malignancies represents an effective approach to building experience, increasing patient volumes and referrals, and fostering development of increased therapeutic options and clinical trials for patients afflicted with otherwise historically neglected cancers.

Managing diabetes in the heat: potential issues and concerns.

OBJECTIVE: To review issues surrounding management of diabetes mellitus during times of extreme high temperatures. METHODS: Materials used for this article were identified through a search of MEDLINE publications from 1966 to 2009. We chose English-language articles by using terms that cross-referenced diabetes mellitus, hot temperature, heat, desert, and insulin. RESULTS: Persons with diabetes may have greater susceptibility to adverse effects from heat (ie, increased number of emergency department visits and hospitalizations, increased occurrence of dehydration and electrolyte abnormalities, and higher death rate) than persons without diabetes. Alterations in glucose homeostasis may occur, and changes in insulin kinetics and stability are possible. The impact of heat exposure on equipment performance (eg, glucometers) must be considered. CONCLUSIONS: Having diabetes places a person at risk for heat-related health problems. Physicians must be aware of possible complications that diabetic patients may encounter in summer heat to prevent problems. Patient educational materials should be developed relating to self management skills in the heat, and the topic should be included in standard diabetes education programs when applicable.

Obesity, abdominal obesity, and insulin resistance.

The correlation of body mass index (BMI) with both adiposity and risk for type 2 diabetes mellitus (DM) is positive. An elevated BMI is also associated with increased mortality from cardiovascular disease (CVD). However, for any given BMI measurement, some persons are at risk for type 2 DM and CVD, while others are not. This disparity of risk may relate to differences in age, fitness, and body composition, including body fat. Obesity- excess body fat- is associated with insulin resistance. Abdominal obesity, in particular, places people at higher risk for developing insulin resistance and, consequently, is associated with an increased risk for type 2 DM and CVD. The association between obesity and insulin resistance is largely due to changes in the function of adipose tissue, specifically, increased release of free fatty acids and abnormalities in adipokine secretion. The properties of visceral adipose tissue may cause these dysfunctions to become magnified. Weight loss has the potential to improve insulin sensitivity through alterations in adipose tissue function.