Clinics and Practice 2018; volume 8:1007

Primary (autoimmune polyglandular syndrome type presenting as basal ganglia 1), or genetic abnormalities (as isolated Correspondence: Edite R.S. Marques Mendes, mutations or as part of complex genetic Department of Medicine - Medicine 1, Unit of secondary to syndromes) are some examples of primary Alto Minho, Santa Luzia Hospital, Viana do extreme hypoparathyroidism causes. Other acquired Castelo, Portugal. causes include radiotherapy or infiltrative Tel.: +351258808366. E-mail: [email protected] Edite Marques Mendes,1 disease (Wilson’s disease, hemochromato- Lúcia Meireles-Brandão,1 sis, metastatic cancer). However, its specif- Key words: Primary hypoparathyroidism; ic cause cannot always be promptly identi- Carla Meira,2 Nuno Morais,2 hypocalcemia; basal ganglia . fied.2-5 Carlos Ribeiro,1 Diana Guerra1 Since is a key cal- Acknowledgments: the authors would like to 1 Department of Medicine - Medicine 1; cium-regulating hormone essential for cal- thank Sara Tavares for her assistance with and 2Department of Medicine - cium homeostasis, metabolic dysfunction in manuscript preparation. Intermediate Care Unit, Unit of Alto hypoparathyroidism originate hyperphos- Contributions: EMM, primary author and Minho, Santa Luzia Hospital, Viana do phatemia and consequently elevated serum patient care; CR, CM, NM, case diagnosis and Castelo, Portugal calcium-phosphorus product, resulting in article review; LM-B, DG, article review. ectopic soft tissue calcifications. Although rarely seen, intracerebral calcifications usu- Conflict of interest: the authors declare no ally deposit in the lentiform (putamen and potential conflict of interest. Abstract globus pallidus) and the caudate nuclei of the basal ganglia. Other organs can be Received for publication: 17 July 2017. Hypoparathyroidism is a rare endocrine affected, more frequently kidneys (present- Revision received: 6 October 2017. Accepted for publication: 11 October 2017. disorder characterized by low serum calci- ing as nephrolithiasis or nephrocalcinosis), um and parathyroid hormone levels. The but can also be seen in joints, eyes This work is licensed under a Creative most common cause is parathyroid iatro- (cataract), skin, vasculature, and other Commons Attribution NonCommercial 4.0 genic surgical removal. However, innumer- organ systems.4,5 Primary hypoparathy- onlyLicense (CC BY-NC 4.0). ous and rarer conditions can cause roidism can cause a wide spectrum of man- hypoparathyroidism. The authors describe a ifestations, mainly due to low serum calci- ©Copyright E.M. Mendes et al., 2018 27-year-old man that presented in emer- um effect on internal organs, and directly Licensee PAGEPress, Italy gency department with confusion, amnesia correlates with the rate of developmentuse of Clinics and Practice 2018; 8:1007 doi:10.4081/cp.2018.1007 and decreased attention span. A cerebral hypocalcemia. Acute and chronic hypocal- computed tomography revealed bilateral cemia classically presents with and extensive calcification in the basal ganglia. may be clinically asymptomatic or present A complete work-up revealed low serum with trivial symptoms. Conversely, it may ality deterioration leading to lifestyle calcium, high serum phosphorus and low manifest as a medical emergency, mainly changes over the past two years. In the past parathyroid hormone, leading to the diagno- due to neurologic and cardiovascular life- 4 months, gradually decreasing organization- sis of idiopathic primary hypoparathy- threatening complications. al skills, and decreased attention span was roidism. Initial intravenous therapy with In this case not only a rare condition noticeable by his parents, although initially calcium gluconate and calcitriol was admin- was diagnosed but also it presented exuber- depreciated by the patient and interpreted as istered, with clinical and analytical ant cerebral involvement with extreme work-related fatigue. improvement. The authors describe a rare hypocalcemia that did not directly correlate An extensive medical history including condition, with an exuberant cerebral pres- commercialto the severity of symptoms. Written familiar history was additionally per- entation and extreme hypocalcemia, which informed consent has been obtained from formed. He had no history of neck surgery, did not directly correlate to the severity of the patient for publication of the submitted seizure, head trauma, fever or headache. symptoms. Not only this is a treatable disor- article and accompanying images. There was no family history of similar der that may have catastrophic results if problems, other autoimmune endocrino - overlooked but also its symptomsNon may be pathies, immunodeficiencies or other con- completely reversed with prompt treatment. Case Report genital defects. On physical examination, vital signs were normal (blood pressure The authors present a case of a previ- 120/85 mmHg, pulse 75 beat/min, respira- Introduction ously healthy 27-year-old male civil engi- tory rate 15/min, and body temperature: neer who was brought to the emergency 36.8ºC). Neurological exam revealed dis- Primary hypoparathyroidism is a rare department due to memory impairment and orientation, with no focal deficits or endocrine disorder characterized by decreased attention span with onset early meningism. Both Chvostek’s and hypocalcemia due to absence or deficient that day. He referred partial amnesia con- Trousseau’s signs were positive. There were production of parathyroid hormone (PTH) cerning activities such as working and driv- no dysmorphic features, mucocutaneous by parathyroid glands. The most common ing, limited to the admission day, accompa- candidiasis, or vitiligo. Respiratory, cardio- cause of primary hypoparathyroidism is nied by perioral numbness and hand and vascular, and abdominal examinations were inadvertent damage to the parathyroid feet paresthesias, but no other symptoms. unremarkable. Ophthalmological evalua- glands during thyroid surgery, constituting The patient did not perceive any other tion with fundoscopy revealed incipient 75% of all cases.1 Non-iatrogenic causes are memory impairment and denied previous opacity in left lens and excluded papillede- scarcer, and comprise congenital or neurological or other symptoms. However, ma. Laboratory testing revealed ionized cal- acquired diseases. Destruction of parathy- contrary to his report, his parents described cium of 0.26 mmol/L (normal range: 1.13- roid gland due to autoimmune disorders hyperirritability, fatigue and overall person- 1.32 mmol/L), serum calcium of 4.6 mg/dL

[Clinics and Practice 2018; 8:1007] [page 5] Case Report

(normal range: 8.6-10.3 mg/dL), albumin of He was discharged with long-term oral nephrolithiasis and/or nephrocalcinosis in 4.5 g/dL (normal range: 3.5-5.2 g/dL), carbonate calcium 3 g per day and calcitriol renal echography were identified. serum phosphorus of 6.4 mg/dL (normal 1mcg per day. range: 2.5-4.9 mg/dL). Further laboratory The patient remained asymptomatic testing revealed decreased parathyroid hor- with no clinical symptoms of numbness, mone (PTH) level (4.6 pg/mL, normal paresthesias more than 2 years after the ini- Discussion and Conclusions range: 15-85 pg/mL) and normal serum tial diagnose. Neurologic and psychiatric Primary hypoparathyroidism is charac- magnesium, serum alkaline phosphatase symptoms were not observed on follow-up terized by an abnormally low level of secre- and serum 25-OH-vitamin D. Kidney func- appointments. Ionized calcium levels per- tion of PTH, a vital importance hormone in tion and serum protein levels were normal. sisted on the lower limit of the reference calcium balance and homeostasis. The Electrocardiographic examination revealed range as targeted, and no evidence of hyper- severity and rate of development of flat T waves and prolonged QT intervals. calciuria in 24 h-urine collection or hypocalcemia determine its clinical mani- Echocardiogram was normal and excluded ventricle dysfunction. A cerebral computed tomography was performed and revealed extensive bilateral and symmetrical calcification in the basal ganglia, thalamus and subcortical cerebral white matter (Figure 1). Additional laboratory work-up showed negative antinuclear antibodies (ANA) and antineutrophil cytoplasmic antibodies (ANCA’s), negative HIV test, as well as normal cortisol and ACTH levels; thyroid antibodies (anti-peroxidase and anti- only tiroglobulin) and adrenal (anti-21 hydroxy- lase) antibodies were performed and were both negative. Thyroid function was also unremarkable. No pathology was observed in ultrasonography of thyroid and parathy- use roid glands. To exclude hypercalciuria a 24- h urine collection was performed and revealed normal urinary calcium (186 mg/24 h with normal range 100-300 mg/24 h), urinary phosphorus and creatinine lev- els. A diagnosis of primary hypoparathy- roidism was done. He was initially admitted Figure 1. Cerebral CT scan revealing extensive bilateral and symmetrical calcification in to an intermediate care unit under continu- the basal ganglia, thalamus and subcortical cerebral white matter. ous electrocardiographic monitoring. Therapy with intravenous calcium glu- conate and vitamin D (cholecalciferol) sup- plementation was immediately initiated. An commercial improvement of his overall condition prompted a switch from intravenous to oral therapy after the first week of treatment. Ionized calcium gradually increased,Non with concomitant decrease in serum phosphorus (Figure 2). During hospitalization, signifi- cant clinical improvement was observed, with dramatical regression of neuromuscu- lar symptoms on the first days of treatment. Nonetheless, although improved, neuropsy- chiatric symptoms were slower to perish, with memory impairment and decreased attention span still present at discharge. A cause for hypoparathyroidism was not encountered, confirming the suspected diagnosis of idiopathic primary hypoparathyroidism, with a presumable autoimmune basis. As complications, exten- sive basal ganglia calcifications and incipi- ent left catarac were identified. He had also a prolonged QT interval, but other cardiac Figure 2. Serum electrolytes levels variation during hospitalization. complications were excluded.

[page 6] [Clinics and Practice 2018; 8:1007] Case Report festations. Acute hypocalcemia classically times lower than the low-normal range of treatment is the same, an alternative therapy results in severe symptoms including laryn- ionized calcium, associated with low levels for patients whose calcium levels are not gospasm, stridor, airway obstruction, neuro- of parathyroid hormone and high levels of controlled by standard therapy was recently muscular irritability, cognitive impairment, phosphorus, consistent with the diagnosis approved by Food and Drug Administration prolonged QT interval, cardiac arrhythmias, of primary hypoparathyroidism. Other with a daily subcutaneous injection of and in rare cases, depressed systolic func- potential hypoparathyroidism causes were recombinant human PTH (PTH 1-84).10 tion and heart failure. Neuromuscular man- extensively studied and excluded. Unfortunately, due to financial restrictions, ifestations include circumoral numbness, A cerebral computed tomography (CT) the drug was not available to administer in paresthesia, hyperreflexia, muscle cramp- scan is required to exclude cerebral compli- our patient. In conclusion, when dealing ing, tetany, and even seizures. cations of hypoparathyroidism. Basal gan- with a patient with neurological symptoms, Hyperreflexia is manifested by carpal glia calcification (BGC), also known in including mild or nonspecific symptoms, spasms (Trousseau sign) and facial spasms Fahr’s syndrome, is a rare presentation in the possibility of basal ganglia calcification (Chvostek sign). Other clinical manifesta- hypoparathyroidism and results due to secondary to hypoparathyroidism, although tions include neuropsychiatric symptoms chronic deposition of calcium-phosphorus rare, should be taken into consideration. such as fatigue, hyperirritability, anxiety complex in cerebral tissue. Its pathogenesis Benign clinical outcome with prompt treat- and depression.6 Chronic hypocalcemia is unknown, and the factors that predispose ment is possible even in patients with may present with symptoms secondary to individuals to basal ganglia calcification extreme calcium depletion and life-threat- deposition of ectopic calcium-phosphorus have not been identified.7 A wide range of ening complications. complex, such as extrapyramidal symptoms other pathologies can cause BGC, thus it is (parkinsonism), dementia and cerebellar particularly important to identify the under- dysfunction, usually seen in intracranial cal- lying condition when upon such a discovery cifications. However, patients with remark- in cerebral CT scan. Apart from References ably low levels of ionized calcium may be hypoparathyroidism and pseudohy- 1. Abate EG, Clarke BL. Review of clinically asymptomatic or present with poparathyroidism, other metabolic, infec- hypoparathyroidism. Front Endocrinol trivial and initially neglected symptoms. tious and genetic diseases, as well as toxic only2016;7:172. Other rarer manifestations of chronic conditions should also be considered as dif- 2. Betterle C, Garelli S, Presotto F. hypocalcemia include dental abnormalities ferential diagnosis in basal ganglia calcifi- 8 Diagnosis and classification of autoim- and ectodermal manifestations, more fre- cations. The treatment of hypoparathy- mune parathyroid disease. Autoimmun quently observed in congenital disorders. roidism is directed toward the severityuse of Revi 2014;13:417-22. Furthermore, patients with hypoparathy- symptoms and the level of serum calcium, 3. Clarke BL, Brown EM, Collins MT, et roidism typically have higher bone density mostly based on calcium supplementation al. Epidemiology and diagnosis of due to low bone turnover, although the risk and the use of vitamin D analogs. Thiazide- hypoparathyroidism. J Clin Endocrinol of fractures is not yet certain. In this report, type diuretics and sodium restriction may Metab 2016;101:2284-99. neurologic symptoms were so unspecific be added to reduce urine calcium if hyper- 4. Mitchell DM, Regan S, Cooley MR, et 4,5,9 that were initially neglected, requiring sev- calcuria is present. al. Long-term follow-up of patients eral years to be perceptible. Acute and long-term management of with hypoparathyroidism. J Clin A diagnosis of primary hypoparathy- hypoparathyroidism should target goal Endocrinol Metabo 2012;97:4507-14. roidism is made based upon identification serum calcium within the low-normal 5. Brandi ML, Bilezikian JP, Shoback D, of characteristic symptoms, a detailed range, with serum phosphorus within the et al. Management of hypoparathy- patient history, a thorough clinical evalua- high-normal range, and avoid significant roidism: summary statement and guide- 1-4 tion and a variety of specialized tests. commercialhypo- or hypercalcemia. The aim is to lines. J Clin Endocrinol Metab Physical examination includes evaluation reduce symptoms and reduce the risk of 2016;101:2273-83. for anterior neck for signs of previous sur- potential life-threatening complications, 6. Bilezikian JP, Khan A, Potts JT Jr, et al. gery, signs of neuromuscular irritability such as cardiac arrhythmias and seizures. Hypoparathyroidism in the adult: epi- (Chvostek’s, Trousseau’s sign), and muco- Long-term management objectives also demiology, diagnosis, pathophysiology, cutaneous candidiasis or vitiligoNon that may concerns the risk of excessive high levels of target-organ involvement, treatment, suggest autoimmune polyglandular syn- serum calcium, including additional ectopic and challenges for future research. J drome type 1. In addition, growth retarda- soft tissue deposition, such as nephrolithia- Bone Miner Res 2011;26:2317-37. tion, congenital anomalies, hearing loss, or sis or nephrocalcinosis, and kidney dys- 7. Shoback D. Hypoparathyroidism. N mental retardation suggest the possibility of function, complication commonly seen in Engl J Med 2008;359:391-403. genetic syndromic as causes for the patients treated for hypoparathyroidism. 8. Basak, RC. A case report of basal gan- disease.1 Thereby, it is of utmost importance routine glia calcification - a rare finding of Blood tests reveal low serum levels of vitamin D, phosphorous, and calcium mon- hypoparathyroidism. Oman Med J calcium and elevated serum phosphorus, itoring, as well as renal calcium excretion 2009;24:220-2. with low levels of parathyroid hormone. evaluation.9 9. Bollerslev J, Rejnmark L, Marcocci C, Twenty-four-hour urine calcium is most In the reported case, this intricate bal- et al. European Society of often increased, but may be normal or low ance was obtained with oral carbonate cal- Endocrinology Clinical Guideline: before calcium supplementation is started, cium 3 g daily and calcitriol 1 mcg daily. treatment of chronic hypoparathy- depending on calcium intake and bone Although formerly said that roidism in adults. Eur J Endocrinol turnover. It is important to exclude condi- hypoparathyroidism was the only classic 2015;173:G1-G20. tions like hypomagnesaemia, vitamin-D endocrine disease where the hormonal 10. Cusano NE, Rubin MR, Bilezikian JP. resistance or deficiency, and renal failure as insufficiency was not treated by substitution PTH(1-84) replacement therapy for the the cause of the biochemical abnormalities.4 of the missing hormone,9 this is currently treatment of hypoparathyroidism. Exp In our patient, calcium levels were four not entirely true. Despite the mainstream of Rev Endocrinol Metab 2015;10:5-13.

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