Diabetes Insipidus: Causes

Pathogenesis (disease development)

Diabetes insipidus is a disorder in hydrogen metabolism that results in increased water excretion due to impaired concentrating ability of the kidneys. Diabetes insipidus can be divided into two forms:

  • Diabetes insipidus centralis is due to an absolute deficiency of the hormone ADH (antidiuretic hormone).Occurrence either idiopathic (“without apparent cause”) or development secondary to damage to the pituitary gland (pituitary gland) or its neighboring structures.
  • Diabetes insipidus renalis is due to a relative deficiency, i.e., insufficient or absent response of the kidneys (in this case, collecting tube and distal tubule) to ADH.

The ability to concentrate urine is lost when the secretion or action of ADH decreases by more than 80%.

Etiology (causes) of diabetes insipidus centralis

Biographic causes

  • Genetic burden from parents, grandparents (mutation in ADH gene; inherited autosomal-dominant) → cell death of ADH-producing neurons.

Disease-related causes.

Congenital malformations, deformities, and chromosomal abnormalities (Q00-Q99).

  • Congenital malformations (malformations)

Blood-forming organs – immune system (D50-D90).

  • Sarcoidosis – granulomatous inflammation; it is considered an inflammatory multisystem disease whose cause is still unclear.

Endocrine, nutritional, and metabolic diseases (E00-E90).

  • Sheehan syndrome – form of anterior pituitary insufficiency (weakness of the pituitary gland) that can occur in women after childbirth.

Cardiovascular system (I00-I99).

Infectious and parasitic diseases (A00-B99).

  • Neurolues (neurosyphilis) – set of symptoms referred to that may occur with a latency period of years to decades in untreated or uncured human syphilis disease.
  • Toxoplasmosis – infectious disease caused by Toxoplasma gondii.

Musculoskeletal system and connective tissue (M00-M99).

  • Granulomatosis with polyangiitis (GPA), formerly Wegener’s granulomatosis – necrotizing (tissue dying) vasculitis (vascular inflammation) of the small to medium-sized vessels (small-vessel vasculitides), which is associated with granuloma formation (nodule formation) in the upper respiratory tract (nose, sinuses, middle ear, oropharynx) as well as the lower respiratory tract (lungs)
  • Lupus erythematosus – systemic disease affecting the skin and connective tissue of the vessels, leading to vascular inflammation (vasculitides) of numerous organs such as the heart, kidneys or brain.
  • Scleroderma – group of diseases belonging to the collagenoses with an unclear cause, which is associated with a connective tissue hardening of the skin and internal organs.

Neoplasms – tumor diseases (C00-D48).

  • Dysgerminoma – malignant (malignant) tumor of the ovary (ovary) and belongs to the malignant germ cell tumors of women.
  • Histiocytosis/Langerhans cell histiocytosis (abbreviation: LCH; formerly: histiocytosis X; Engl. histiocytosis X, langerhans-cell histiocytosis) – systemic disease with proliferation of Langerhans cells in different tissues (skeleton 80% of cases; skin 35% and pituitary gland 25%, lung and liver 15-20%); in rare cases neurodegenerative signs may also occur; in 5-50 % of cases, diabetes insipidus (hormone deficiency-related disturbance in hydrogen metabolism, leading to extremely high urine excretion) occurs when the pituitary gland is affected; the disease usually manifests itself only in adulthood; prevalence (disease frequency) approx. 1-2 per 100,000 inhabitants
  • Malignant neoplasms of the blood system such as leukemia (blood cancer) or lymphoma (neoplasm originating from the lymphatic system).
  • Granulomas (nodular neoplasms) such as histiocytosis X 1(see above) or xanthoma disseminatum.
  • Craniopharyngeoma – benign (benign) tumor of the skull base arising from epithelial remnants of Rathke’s pouch; Rathke’s pouch gives rise to the anterior lobe of the pituitary gland (pituitary gland) during embryonic development.
  • Leukemia (blood cancer)
  • Lymphoma – malignant neoplasm originating from the lymphatic system.
  • Meningiomas – brain tumors/most common tumors of the central nervous system.
  • Metastases (daughter tumors) to the head, unspecified (lung, mammary/female breast).
  • Neoplasms in the area of the head, unspecified.
  • Suprasellar pituitary adenoma
  • Tumor or cyst of the pituitary gland or hypothalamus.
  • Disruption of the pituitary stalk due to trauma (e.g., traumatic brain injury (TBI), brain surgery) → ADH cannot be transported to the anterior pituitary lobe (HVL)

Psyche – nervous system (F00-F99; G00-G99).

Pregnancy, childbirth and puerperium (O00-O99)

  • Pregnancy

Injuries, poisonings, and other consequences of external causes (S00-T98).

  • Head injuries, unspecified

Operations

  • Pituitary surgery (surgery of the pituitary gland).

Environmental stress – intoxications (poisoning).

  • Tetrodotoxin – poison of the buffer fish.
  • Snake venom

Other causes

  • Idiopathic: autoimmune antibodies against ADH-producing cells.
  • [Alcohol abuse (alcohol temporarily inhibits ADH secretion, leading to excessive fluid loss)]
  • Surgical intervention on the pituitary gland (pituitary gland).

Etiology (causes) of renal diabetes insipidus

Biographic causes

  • Genetic burden from parents, grandparents.
  • Genetic diseases
    • Sickle cell anemia (med: drepanocytosis; also sickle cell anemia, English : sickle cell anemia) – genetic disorder with autosomal recessive inheritance affecting erythrocytes (red blood cells); it belongs to the group of hemoglobinopathies (disorders of hemoglobin; formation of an irregular hemoglobin called sickle cell hemoglobin, HbS).

Disease-related causes

Congenital malformations, deformities and chromosomal abnormalities (Q00-Q99).

  • Mutations in the gene for the V2 receptor (X-linked) or the corresponding aquaporin (usually autosomal) [most common cause in children].

Blood-forming organs – immune system (D50-D90).

  • Sarcoidosis – granulomatous inflammation; it is considered an inflammatory multisystem disease whose cause is still unclear.

Endocrine, nutritional, and metabolic diseases (E00-E90).

  • Amyloidosis – extracellular (“outside the cell”) deposits of amyloids (degradation-resistant proteins) that can lead to cardiomyopathy (heart muscle disease), neuropathy (peripheral nervous system disease), and hepatomegaly (liver enlargement), among other conditions.
  • Hypercalcemia (excess calcium).
  • Hypercalciuria (increased excretion of calcium in the urine).
  • Hyperkalemia (excess potassium)

Neoplasms – tumor diseases (C00-D48)

  • Sarcoma – malignant tumor originating from soft tissue.

Psyche – nervous system (F00-F99; G00-G99).

  • Neurosarcoidosis – inflammatory systemic disease affecting the skin, lungs, and in this case, the nervous system.

Pregnancy, childbirth and puerperium (O00-O99).

  • Pregnancy → transient (“temporary”) diabetes insipidus due to increased production of vasopressinases in the placenta (placenta)

Genitourinary system (kidneys, urinary tract – reproductive organs) (N00-N99).

  • Chronic pyelonephritis (inflammation of the renal pelvis).
  • Renal ischemia (acute tubular necrosis) – cell death in the kidney caused by damage from drugs or toxins
  • Renal cysts
  • Obstruction (shifting/clogging) of ureter (ureter) or urethra (urethra)
  • Tubulointerstitial kidney disease – group of kidney diseases that primarily involve the renal interstitium (tissue formed that lies between the nephrons (smallest filtration units of the kidney) and contains arteries, veins, nerves, and connective tissue) including the tubular apparatus

Laboratory diagnoses – laboratory parameters that are considered independent risk factors.

  • Hypercalcemia (excess calcium).
  • Hypokalemia (potassium deficiency)

Medication