Diagnosis and treatment of hypoparathyroidism: a position statement from the Brazilian Society of Endocrinology and Metabolism

Maeda, Sergio Setsuo; Moreira, Carolina Aguiar; Borba, Victória Zeghbi Cochenski; Bandeira, Francisco; Farias, Maria Lucia Fleiuss de; Borges, João Lindolfo Cunha; Paula, Francisco José Albuquerque de; Vanderlei, Felipe Augusto Brasileiro; Montenegro, Fábio Luiz de Menezes; Santos, Rodrigo Oliveira; Ferraz-de-Souza, Bruno; Lazaretti-Castro, Marise

doi:10.20945/2359-3997000000015

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Guideline • Arch. Endocrinol. Metab. 62 (1) • Jan-Feb 2018 • https://doi.org/10.20945/2359-3997000000015 copy

Diagnosis and treatment of hypoparathyroidism: a position statement from the Brazilian Society of Endocrinology and Metabolism

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Objective

To present an update on the diagnosis and treatment of hypoparathyroidism based on the most recent scientific evidence.

Materials and methods

The Department of Bone and Mineral Metabolism of the Sociedade Brasileira de Endocrinologia e Metabologia (SBEM; Brazilian Society of Endocrinology and Metabolism) was invited to prepare a document following the rules set by the Guidelines Program of the Associação Médica Brasileira (AMB; Brazilian Medical Association). Relevant papers were retrieved from the databases MEDLINE/PubMed, LILACS, and SciELO, and the evidence derived from each article was classified into recommendation levels according to scientific strength and study type.

Conclusion

An update on the recent scientific literature addressing hypoparathyroidism is presented to serve as a basis for the diagnosis and treatment of this condition in Brazil.

Keywords
Hypoparathyroidism; hypocalcemia; calcitriol; PTH; guideline; diagnosis; treatment

	Total calcium	Ionic calcium	PTH	Symptoms of hypocalcemia	Bone manifestations	Associated diseases
Hypoalbuminemia	Low	Normal	Normal	Absent	None	Liver cirrhosis, nephrotic syndrome, burn, malnutrition, sepsis
Hypomagnesemia	Low	Low	Variable	Variable	None	Diuretics, chronic diarrhea, small bowel bypass or resection
Calcium deficiency	Low	Low	High	Variable	Rickets/osteomalacia	Severe malnutrition, Roux-en-Y gastric bypass (RYGB)
Vitamin D deficiency	Low	Low	High	Variable	Rickets/osteomalacia increased resorption (decreased density)	Decreased sun exposure, obesity, dark skin, RYGB, aging, severe malnutrition, celiac disease, pancreatic diseases, steatorrhea, antiepileptic drugs
Hyperphosphatemia (acute)	Low	Low	Variable	Variable	Dependent on the etiology	Phosphate-containing enemas, renal failure, intense tissue breakdown (rhabdomyolysis or tumor lysis)
Chronic kidney disease (CKD) and GFR < 30 mL/min/1.73 m²	Low	Variable	High	Variable	Hyperparathyroidism (eventual low turnover)	Severe hypertension, diabetes mellitus, and others
Hungry bone syndrome	Low	Low	Variable	Moderate/severe	Hyperparathyroidism	Surgical cure of hyperparathyroidism (primary or secondary to CKD)
Drugs: Antiresorptives (bisphosphonates, denosumab), calcimimetics (cinacalcet), calcium chelators (EDTA, citrate, foscarnet), antiepileptics (phenytoin, phenobarbital, carbamazepine), proton pump inhibitors, loop diuretics, chemotherapeutic drugs	Low	Low	Variable	Variable	Dependent on the etiology	Osteoporosis, primary or secondary hyperparathyroidism, blood transfusion, epilepsy, peptic ulcer, neoplasias, etc.
Acute pancreatitis	Low	Low	High	Variable	None	Alcohol abuse, gallbladder stones

Reference	Author, year	Country	Prevalence of hypoparathyroidism	Comments
²⁷27. Underbjerg L, Sikjaer T, Mosekilde L, Rejnmark L. Cardiovascular and renal complications to postsurgical hypoparathyroidism: a Danish nationwide controlled historic follow-up study. J Bone Miner Res. 2013;28(11):2277-85.	Underbjerg and cols., 2013	Denmark	22/100,000 (general population)	Data from 1988 to 2012
³³33. Powers J, Joy K, Ruscio A, Lagast H. Prevalence and incidence of hypoparathyroidism in the United States using a large claims database. J Bone Miner Res. 2013;28(12):2570-6.	Powers and cols., 2013	USA	5.0%	120,000 surgeries in one year
³⁵35. Rosato L, Avenia N, Bernante P, De Palma M, Gulino G, Nasi PG, et al. Complications of thyroid surgery: analysis of a multicentric study on 14,934 patients operated on in Italy over 5 years. World J Surg. 2004;28(3):271-6.	Rosato and cols., 2004	Italy	1.7%	15,000 thyroidectomies with a 5-year follow-up
³⁷37. Youngwirth L, Benavidez J, Sippel R, Chen H. Parathyroid hormone deficiency after total thyroidectomy: incidence and time. J Surg Res. 2010;163(1):69-71.	Youngwirth and cols., 2010	USA	0.74%	12% of patients had transient hypoparathyroidism, only 2 required calcitriol in the long term
³⁸38. Snyder S, Govednik C, Lairmore T, Jiang DS, Song J. Total thyroidectomy as primary definitive treatment for Graves’ hyperthyroidism. Am Surg. 2013;79(12):1283-8.	Snyder and cols., 2013	USA	1.0% (for Graves’ disease) 1.8% (for other types of hyperthyroidism) 0% (for other benign diseases)	780 total thyroidectomies for different reasons
³⁹39. Pelizzo MR, Variolo M, Bernardi C, Izuzquiza M, Piotto A, Grassetto G, et al. Complications in thyroid resurgery: a single institutional experience on 233 patients from a whole series of 4,752 homogeneously treated patients. Endocrine. 2014;47(1):100-6.	Pelizzo and cols., 2014	Italy	3.3%	233 patients after a second thyroid surgery
⁴⁰40. Puzziello A, Rosato L, Innaro N, Orlando G, Avenia N, Perigli G, et al. Hypocalcemia following thyroid surgery: incidence and risk factors. A longitudinal multicenter study comprising 2,631 patients. Endocrine. 2014;47(2):537-42.	Puzziello and cols., 2014	Italy	0.9%	2,631 thyroidectomies 28.8% had transient hypocalcemia
⁴¹41. Ritter K, Elfenbein D, Schneider DF, Chen H, Sippel RS. Hypoparathyroidism after total thyroidectomy: incidence and resolution. J Surg Res. 2015;197(2):348-53.	Ritter and cols., 2015	USA	1.9%	1,054 thyroidectomies
⁴²42. Wei T, Li Z, Jin J, Chen R, Gong Y, Du Z, et al. Autotransplantation of Inferior Parathyroid glands during central neck dissection for papillary thyroid carcinoma: a retrospective cohort study. Int J Surg. 2014;12(12):1286-90.	Wei and cols., 2014	China	0.9% (3/321) – autotransplantation 3.8% (6/156) – parathyroid glands preserved in place	477 thyroidectomies with (n = 321) and without (n = 156) parathyroid autotransplantation
⁴³43. Ito Y, Kihara M, Kobayashi K, Miya A, Miyauchi A. Permanent hypoparathyroidism after completion total thyroidectomy as a second surgery: How do we avoid it? Endocr J. 2014;61(4):403-8.	Ito and cols., 2014	Japan	8%	154 completion thyroidectomies after a previous thyroidectomy
⁴⁴44. Lorente-Poch L, Sancho JJ, Ruiz S, Sitges-Serra A. Importance of in situ preservation of parathyroid glands during total thyroidectomy. Br J Surg. 2015;102(4):359-67.	Lorente-Poch and cols., 2015	Spain	4.6%	657 thyroidectomies, 1-year follow-up
⁴⁵45. Nawrot I, Pragacz A, Pragacz K, Grzesiuk W, Barczyński M. Total thyroidectomy is associated with increased prevalence of permanent hypoparathyroidism. Med Sci Monit. 2014;20:1675-81.	Nawrot and cols., 2014	Poland	8.5%	401 thyroidectomies
⁴⁶46. Järhult J, Andersson PO, Duncker L. Alternating from subtotal thyroid resection to total thyroidectomy in the treatment of Graves’ disease prevents recurrences but increases the frequency of permanent hypoparathyroidism. Langenbecks Arch Surg. 2012;397(3):407-12.	Järhult and cols., 2012	Sweden	6% of the total thyroidectomies	265 thyroidectomies in patients with Graves’ disease
⁴⁷47. Dedivitis RA, Pfuetzenreiter Jr EG, Nardi CE, Barbara EC. Prospective study of clinical and laboratorial hypocalcemia after thyroid surgery. Braz J Otorhinolaryngol. 2010;76(1):71-7.	Dedivitis and cols., 2010	Brazil	6.6%	91 thyroidectomies, 6 patients had biochemical hypoparathyroidism after 1 month
⁴⁸48. Accetta P, Accetta I, Accetta AC, Araujo MS, Accetta R, Campos KB. Total thyroidectomy for benign thyroid diseases. Rev Col Bras Cir. 2011;38(4):223-6.	Accetta and cols., 2011	Brazil	0/66 – no case	66 thyroidectomies
⁴⁹49. Vanderlei FA, Vieira JG, Hojaij FC, Cervantes O, Kunii IS, Ohe MN, et al. Parathyroid hormone: an early predictor of symptomatic hypocalcemia after total thyroidectomy. Arq Bras Endocrinol Metabol. 2012;56(3):168-72.	Vanderlei and cols., 2012	Brazil	2.5%	40 thyroidectomies
⁵⁰50. Molinari AS, Treiguer A, Gava VG, Rojas JL, Evangelista PE, Goncalves I, et al. Thyroid surgery performed on an overnight basis: a 17 years of experience. Arch Endocrinol Metab. 2015;59(5):434-40.	Molinari and cols., 2015	Brazil	0.3%	3,411 thyroidectomies
⁵¹51. Ywata de Carvalho A, Chulam TC, Kowalski LP. Long-term Results of Observation vs Prophylactic Selective Level VI Neck Dissection for Papillary Thyroid Carcinoma at a Cancer Center. JAMA Otolaryngol Head Neck Surg. 2015;141(7):599-606.	Ywata de Carvalho and cols., 2015	Brazil	11.8% of patients with central neck dissection 2.3% of patients without central neck dissection	Two different groups: total thyroidectomy with (n = 106) and without central neck dissection (n = 478)
⁵²52. Montenegro FL, Lourenço DM Jr, Tavares MR, Arap SS, Nascimento CP Jr, Massoni Neto LM, et al. Total parathyroidectomy in a large cohort of cases with hyperparathyroidism associated with multiple endocrine neoplasia type 1: experience from a single academic center. Clinics (Sao Paulo). 2012;67 Suppl1:131-9.	Montenegro and cols., 2012	Brazil	28%	83 patients with hyperparathyroidism due to MEN-1/all with parathyroid autotransplantation

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E-mail: aem.editorial.office@endocrino.org.br

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[1] Correspondence to: Sergio Setsuo Maeda Rua Ministro Gastão Mesquita, 250, ap. 307 05012-010 – São Paulo, SP, Brasil ssetsuo@terra.com.br

Hypoparathyroidism due to PTH deficiency	Parathyroid destruction	Following cervical surgery
		Cervical radiotherapy or radioiodine therapy
		Autoimmune: isolated or associated with polyglandular disease [AIRE]
		Parathyroid infiltration by neoplastic, granulomatous, or storage diseases (Wilson's disease and hemochromatosis)
		Riedel's thyroiditis
	Genetic diseases affecting parathyroid development and/or PTH production	Isolated hypoparathyroidism [PTH, GCM2, SOX3]
		Genetic syndromes associated with hypoparathyroidism (e.g. DiGeorge, CHARGE, Kenny-Caffey, Sanjad-Sakati, HDR, etc.) [TBX1, NEBL, GATA3, TBCE, FAM111A, CHD7, SEMA3E]
		Mitochondrial diseases
	Regulation change in PTH secretion	Autosomal dominant hypocalcemia type 1 [CASR] and type 2 [GNAS11]
		Activating anti-CASR antibodies
		Chronic hypomagnesemia and hypermagnesemia
Functional hypoparathyroidism due to peripheral resistance to PTH action	Pseudohypoparathyroidism	Genetic defects in PTH post-receptor signaling [GNAS, STX16, NESP55, PRKAR1A, PDE4D]