ImportanceA combination of diabetes, coronary heart disease (CHD), and stroke has multiplicative all-cause mortality risk compared with any individual morbidity in White populations, but there is a lack of studies in Black populations in the US.ObjectiveTo examine the association of cardiometabolic multimorbidity (diabetes, stroke, and CHD) individually and collectively with all-cause and CHD mortality.Design, Setting, and ParticipantsThis cohort study included Black adults in the Jackson Heart Study followed over a median of 15 years. Baseline examinations were performed between 2000 and 2004, with follow-up on all-cause and CHD mortality through May 31, 2018. Participants were categorized into mutually exclusive groups at baseline: (1) free of cardiometabolic morbidity, (2) diabetes, (3) CHD, (4) stroke, (5) diabetes and stroke, (6) CHD and stroke, (7) diabetes and CHD, and (8) diabetes, stroke, and CHD. Data were analyzed from 2019 to 2021.ExposureCardiometabolic disease alone or in combination.Main Outcomes and MeasuresThe main outcomes were all-cause mortality and CHD mortality. Cox models estimated hazard ratios (HRs) with 95% CIs adjusted for sociodemographic and cardiovascular risk factors.ResultsAmong 5064 participants (mean [SD] age, 55.4 [12.8] years; 3200 [63%] women) in the Jackson Heart Study, 897 (18%) had diabetes, 192 (4%) had CHD, and 104 (2%) had a history of stroke. Among participants with cardiometabolic morbidities, the crude all-cause mortality rates were lowest for diabetes alone (24.4 deaths per 1000 person-years) and highest for diabetes, CHD, and stroke combined (84.1 deaths per 1000 person-years). For people with only 1 cardiometabolic morbidity, risk for all-cause mortality was highest for people with stroke (HR, 1.74; 95% CI, 1.24-2.42), followed by CHD (HR, 1.59 (95% CI, 1.22-2.08) and diabetes (HR, 1.50; 95% CI, 1.22-1.85), compared with no cardiometabolic morbidities. There were also increased risks of mortality with combinations of diabetes and stroke (HR, 1.71; 95% CI, 1.09-2.68), CHD and stroke (HR, 2.23; 95% CI, 1.35-3.69), and diabetes and CHD (HR, 2.28; 95% CI, 1.65-3.15). The combination of diabetes, stroke, and CHD was associated with the highest all-cause mortality (HR, 3.68; 95% CI, 1.96-6.93). Findings were similar for CHD mortality, but with a larger magnitude of association (eg, diabetes, stroke, and CHD: HR, 13.52; 95% CI, 3.38-54.12).Conclusions and RelevanceIn this cohort study, an increasing number of cardiometabolic multimorbidities was associated with a multiplicative increase in risk of all-cause mortality among Black adults, with a greater magnitude of association for CHD mortality.

Pituitary hyperplasia is defined as an absolute increase in the number of one or more adenohypophyseal cell subtypes, manifesting radiologically as pituitary enlargement beyond what is considered normal. It has been noted in certain physiological conditions like pregnancy however can also be seen in pathological conditions with end organ insufficiency like severe hypothyroidism. 21- year old female with a past medical history of Primary Hypothyroidism secondary to Hashimoto’s thyroiditis presented initially for evaluation of worsening headache and blurry vision. She was diagnosed with hypothyroidism at 10 years of age and had an extensive family history of hypothyroidism. At the time of presentation, she was 11 months post- partum and had been on and off her levothyroxine supplementation, having stopped it completely for a few months after delivery. MRI brain showed an 18 mm homogeneously enhancing intrasellar mass with suprasellar extension. She was referred to Neurosurgery for further evaluation. Workup revealed a TSH >100 (0.27 - 4.2 mIU/L) and FT4 <0.4 (0.8 - 2 ng/dL). In the context of severe untreated hypothyroidism and MRI findings consistent with pituitary hyperplasia with abutment but no mass effect on the optic apparatus, initial plan was to treat the hypothyroidism medically and observe closely. Patient was started on levothyroxine supplementation. Her TSH improved to 3.367 (0.550 - 4.780 uIU/mL) and FT4 to 2.00 (0.89 - 1.76 ng/dL), ηοωεϖερ she continued to have worsening of visual symptoms. Surgery was considered to decompress the optic nerve, but pre-operative MRI showed a significant decrease in size of the pituitary gland with decreased suprasellar bulging and no mass effect on the optic chiasm. Surgery was subsequently cancelled. Prolonged primary hypothyroidism leads to pituitary hyperplasia due to loss of negative feedback from lack of circulating T4 and T3, leading to excessive TRH secretion from the hypothalamus. The high TRH can lead to thyrotroph as well as lactotroph hyperplasia. Subsequently patients can present with headache, vision changes along with signs and symptoms of hypothyroidism and increased prolactin secretion. It is important to differentiate hyperplasia from other sellar lesions like pituitary macroadenoma or hypophysitis. Patients with hypothyroidism, who have pituitary enlargement diagnosed on brain imaging, should be promptly diagnosed and treated with thyroid hormone replacement. With a higher frequency and improved quality of imaging techniques, we are increasingly coming across scenarios of abnormal findings on imaging. Correlation of radiographic imaging results with a thorough history and biochemical testing is essential prior to proceeding with surgical intervention.

Autoimmune Polyglandular Syndrome Type 1 (APS-1) is clinically defined as the presence of at least two components of the classic triad of hypoparathyroidism, adrenal insufficiency and mucocutaneous candidiasis. It is commonly seen amongst Finns, Sardinians and Iranian Jews and is a very rare condition, with a challenging set of management. 50-year old female with a known past medical history of Bipolar disorder, Primary Adrenal Insufficiency, Hypothyroidism, Alopecia was transferred from an acute psychiatric facility for medical clearance. Patient was noted to have findings initially suggestive of Subarachnoid Hemorrhage on a CT scan of the Head which was later deemed to be likely dystrophic calcification. During her stay on the medical floors, patient was found to be unresponsive and hypotensive, after a bout of agitation. She had to be urgently intubated and started on stress doses of steroids (Hydrocortisone 100 mg every 8 hours) and was upgraded to the Intensive Care Unit (ICU). Patient was eventually successfully weaned off the ventilator and steroid doses were slowly tapered. During her hospital course she was noted to have gradually decreasing Calcium levels, down to a corrected Calcium level of 7.6. Further workup for the hypocalcemia revealed a Vitamin D Level of 12, and Parathyroid Hormone (PTH) level of 0. Patient was subsequently started on adequate Calcium and Vitamin D supplementation for the same. After a few days when the family was located and contacted through social work support, and a more thorough history was obtained, it was found that one out of the patient’s three sisters had a similar constellation of deficiencies. Patient had previously been diagnosed with a polyendocrine syndrome, however she was irregular with her medication compliance and follow-up outpatient with her endocrinologist due to her persistent psychiatric issues and poor social support. APS-1 is an autosomal recessive disorder caused by mutation in AIRE, the autoimmune regulator gene which is hypothesized to be playing an important role in the generation of regulatory T cells. Although the complete pathogenesis is unclear, mutation in generation of these regulatory cells leads to autoantibody formation. Hypoparathyroidism or Chronic persistent Mucocutaneous Candidiasis is usually the first manifestation seen during adolescence and adrenal insufficiency usually manifests later. A variation of other autoimmune syndromes can be observed, with Hypothyroidism, Type-1 Diabetes Mellitus and Primary Hypogonadism being a few of them. Treatment primarily involves replenishment of the hormones of the underperforming gland. Management of a complex syndrome like APS-1 in a patient with psychiatric disabilities can be challenging and needs a multi-disciplinary approach involving the endocrinologist, the primary care physician and the psychiatrist.