As the overall prevalence of asthma has escalated in the past decades, so has the population of patients with severe asthma. This condition is often difficult to manage due to the relative limitation of effective therapeutic options for the physician and the social and economic burden of the disease on the patient. Management should include an evaluation and elimination of modifiable risk factors such as smoking, allergen exposure, obesity and non-adherence, as well as therapy for co-morbidities like gastro-esophageal reflux disease and obstructive sleep apnea. Current treatment options include conventional agents such as inhalational corticosteroids, long acting β2 agonists, leukotriene antagonists, and oral corticosteroids. Less conventional treatment options include immunotherapy with methotrexate, cyclosporine and tacrolimus, biological drugs like monoclonal antibodies, tumor necrosis factor-α blockers and oligonucleotides, phosphodiesterase inhibitors, antimicrobials and bronchial thermoplasty.

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Background: Adrenals glands are the most commonly involved endocrine organ in cancer metastasis due to its abundant lymphatic communication and blood supply. Up to 4% of non-small-cell lung cancers and 71% of lymphomas have bilateral adrenal metastasis. Early detection with hormone replacement can be life-saving. Clinical Case: A 58 year old male was admitted for hyperkalemia (potassium 6.4 mmol/L, range: 3.5-5.1) with prolonged PR interval on EKG, hyponatremia (sodium 131 mmol/L, range: 136-145), hypoglycemia (glucose 48mg/dl), and renal function impairment (creatinine level elevation of 1.38 mg/dl from a baseline of 0.94 mg/dl). He had been diagnosed with Stage IVb non-small-cell lung cancer about 20 months prior, and had a known history of chemotherapy, adrenal metastasis and left adrenal gland radiation (20 G in 5 daily fractions) about 10 months ago. For the past 10 months, the patient had reported no weight loss, nausea, vomiting, or other symptoms or signs of adrenal insufficiency, apart from intermittent fatigue, which he had attributed to his lung cancer diagnosis. On review, a previous PET/CT scan showed intense FDG uptake in the bilaterally enlarged adrenal glands, measuring 3.3 x 2.8 cm on the left, and 3.1 x 1.8 cm on the right. His ACTH level was found to be elevated to 1,023 pg/ml (range: 6-63) with borderline low free cortisol level 0.06 mcg/dl (range 0.04-0.35). Aldosterone level was found to be 3.4 ng/dl (range: 4-31), with a renin level of 36.2 ng/ml/hr (range: 0.5-4). Primary adrenal insufficiency was diagnosed, and the patient was started on hormone replacement therapy, which was titrated as outpatient. Now he is continued on a regimen of hydrocortisone 15 mg and 5 mg, at 8 am and 3 pm respectively, and fludrocortisone 0.1 mg daily. In two months, his ATCH level fell from 1,023 to 89 pg/ml with normalization of kidney functions, sodium level (now 137 mmol/L) and potassium level (now 4.8 mmol/L). He gained 4 kg, and has been feeling more energetic and functional on his follow up visits. Conclusion: Patients with adrenal metastatic cancer may have atypical symptoms and signs despite having severe primary adrenal insufficiency. High risk patients should be monitored, even in the absence of symptoms, for the development of adrenal insufficiency. Reference: 1. Yamamoto, T. (2018). LATENT ADRENAL INSUFFICIENCY: CONCEPT, CLUES TO DETECTION, AND DIAGNOSIS. Endocrine Practice, 24(8), pp.746-755. 2. Angelousi A, Alexandraki KI, Kyriakopoulos G, et al. Neoplastic metastases to the endocrine glands. Endocr Relat Cancer. 2019.

Background: Hypokalemic periodic paralysis (HPP) related to thyrotoxicosis, though rare, is more often seen in Asian males. Type 1 renal tubular acidosis (T1 RTA), which can also cause HPP, is typically managed with alkali therapy and potassium supplementation, though there are no well-established guidelines for management in pregnancy. Clinical Case: A 27-year-old Puerto Rican woman, at 32 weeks gestation, presented to the hospital with sudden onset muscle weakness, and was found to have 1/5 muscle strength in her lower extremities. She had no personal or family history of similar illness. Laboratory analysis revealed hypokalemia (potassium 2.0 mmol/L, range: 3.5 – 5); non-gap metabolic acidosis (sodium 137mmol/L, range 136 – 145; chloride 113 mmol/L, range 98- 107; and bicarbonate 8 mmol/L, range 22 – 29); and an arterial pH of 7.09. Urine studies demonstrated a urine pH of 6.5 and a urine sodium of 32 mmol/L which was diagnostic of T1 RTA in the context of her metabolic derangements. She was treated emergently with potassium and bicarbonate infusions, with improvement in her symptoms. Subsequent thyroid function testing revealed: a low TSH of 0.01 uIU/ml, normal free T4 of 1.66 (range: 0.9 - 1.7) ng/dl, normal free of T3 3.7 (range: 2.0 -4.4) pg/ml and elevated total T4 of 16.5 (range: 4.5 - 11.7) ug/dl. Renal ultrasound demonstrated medullary nephrocalcinosis. She was discharged on potassium and sodium citrate tablets. At 37 weeks, the patient was readmitted for induction of labor due to pre-eclampsia, and delivered a healthy male baby. Several months later, she presented to the Endocrinology clinic with symptoms of increased frequency bowel movements, palpitations and heat intolerance, which had been ongoing since pregnancy. On review, a metabolic panel prior to pregnancy had demonstrated non-gap acidosis and mild hypokalemia. Further testing demonstrated the following: TSH < 0.01 uIU/ml, Free T4 1.71 ng/dl, Free T3 4.8 pg/ml, TSI 280%, and a thyroid uptake scan with homogenous radiotracer uptake, with a 24-hour uptake of 40%. She was started on methimazole therapy, and continued on potassium and sodium citrate tablets with clinical and biochemical improvement. Conclusion: Thyrotoxicosis can augment hypokalemia in T1 RTA, and can increase the risk of HPP. Our patient had biochemical evidence of RTA prior to pregnancy, though without episodes of HPP, and we believe that her hyperthyroidism, triggered by pregnancy, may have been the additional insult that precipitated her paralysis. This is the first reported case of HPP related to co-existing thyrotoxicosis and T1 RTA in a pregnant individual. Reference:1. Tu ML, Fang YW, Leu JG, Tsai MH. An atypical presentation of high potassium renal secretion rate in a patient with thyrotoxic periodic paralysis: a case report. BMC Nephrol. 2018;19(1):160. Published 2018 Jul 4. doi:10.1186/s12882-018-0971-9